siRNA targeting deubiqutination enzymes

ABSTRACT

Efficient sequence specific gene silencing is possible through the use of siRNA technology. By selecting particular siRNAs by rational design, one can maximize the generation of an effective gene silencing reagent, as well as methods for silencing genes. Methods, compositions, and kits generated through rational design of siRNAs are disclosed including those directed to nucleotide sequences for deubiquitination enzymes.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. Ser. No. 10/714,333, filed Nov. 14, 2003, which claims the benefit of U.S. Provisional Application No. 60/426,137, filed Nov. 14, 2002, and also claims the benefit of U.S. Provisional Application No. 60/502,050, filed Sep. 10, 2003; this application is also a continuation-in-part of U.S. Ser. No. 10/940,892, filed Sep. 14, 2004, which is a continuation of PCT Application No. PCT/US04/14885, international filing date May 12, 2004. The disclosures of the priority applications, including the sequence listings and tables submitted in electronic form in lieu of paper, are incorporated by reference into the instant specification.

SEQUENCE LISTING

The sequence listing for this application has been submitted in accordance with 37 CFR § 1.52(e) and 37 CFR § 1.821 on CD-ROM in lieu of paper on a disk containing the sequence listing file entitled “DHARMA_(—)2100-US79_CRF.txt” created Sep. 28, 2007, 668 kb. Applicants hereby incorporate by reference the sequence listing provided on CD-ROM in lieu of paper into the instant specification.

FIELD OF INVENTION

The present invention relates to RNA interference (“RNAi”).

BACKGROUND OF THE INVENTION

Relatively recently, researchers observed that double stranded RNA (“dsRNA”) could be used to inhibit protein expression. This ability to silence a gene has broad potential for treating human diseases, and many researchers and commercial entities are currently investing considerable resources in developing therapies based on this technology.

Double stranded RNA induced gene silencing can occur on at least three different levels: (i) transcription inactivation, which refers to RNA guided DNA or histone methylation; (ii) siRNA induced mRNA degradation; and (iii) mRNA induced transcriptional attenuation.

It is generally considered that the major mechanism of RNA induced silencing (RNA interference, or RNAi) in mammalian cells is mRNA degradation. Initial attempts to use RNAi in mammalian cells focused on the use of long strands of dsRNA. However, these attempts to induce RNAi met with limited success, due in part to the induction of the interferon response, which results in a general, as opposed to a target-specific, inhibition of protein synthesis. Thus, long dsRNA is not a viable option for RNAi in mammalian systems.

More recently it has been shown that when short (18-30 bp) RNA duplexes are introduced into mammalian cells in culture, sequence-specific inhibition of target mRNA can be realized without inducing an interferon response. Certain of these short dsRNAs, referred to as small inhibitory RNAs (“siRNAs”), can act catalytically at sub-molar concentrations to cleave greater than 95% of the target mRNA in the cell. A description of the mechanisms for siRNA activity, as well as some of its applications are described in Provost et al (2002) Ribonuclease Activity and RNA Binding of Recombinant Human Dicer, EMBO J. 21(21): 5864-5874; Tabara et al. (2002) The dsRNA Binding Protein RDE-4 Interacts with RDE-1, DCR-1 and a DexH-box Helicase to Direct RNAi in C. elegans, Cell 109(7):861-71; Ketting et al. (2002) Dicer Functions in RNA Interference and in Synthesis of Small RNA Involved in Developmental Timing in C. elegans; Martinez et al., Single-Stranded Antisense siRNAs Guide Target RNA Cleavage in RNAi, Cell 110(5):563; Hutvagner & Zamore (2002) A microRNA in a multiple-turnover RNAi enzyme complex, Science 297:2056.

From a mechanistic perspective, introduction of long double stranded RNA into plants and invertebrate cells is broken down into siRNA by a Type III endonuclease known as Dicer. Sharp, RNA interference—2001, Genes Dev. 2001, 15:485. Dicer, a ribonuclease-III-like enzyme, processes the dsRNA into 19-23 base pair short interfering RNAs with characteristic two base 3′ overhangs. Bernstein, Caudy, Hammond, & Hannon (2001) Role for a bidentate ribonuclease in the initiation step of RNA interference, Nature 409:363. The siRNAs are then incorporated into an RNA-induced silencing complex (RISC) where one or more helicases unwind the siRNA duplex, enabling the complementary antisense strand to guide target recognition. Nykanen, Haley, & Zamore (2001) ATP requirements and small interfering RNA structure in the RNA interference pathway, Cell 107:309. Upon binding to the appropriate target mRNA, one or more endonucleases within the RISC cleaves the target to induce silencing. Elbashir, Lendeckel, & Tuschl (2001) RNA interference is mediated by 21- and 22-nucleotide RNAs, Genes Dev. 15:188, FIG. 1.

The interference effect can be long lasting and may be detectable after many cell divisions. Moreover, RNAi exhibits sequence specificity. Kisielow, M. et al. (2002) Isoform-specific knockdown and expression of adaptor protein ShcA using small interfering RNA, J. Biochem. 363:1-5. Thus, the RNAi machinery can specifically knock down one type of transcript, while not affecting closely related mRNA. These properties make siRNA a potentially valuable tool for inhibiting gene expression and studying gene function and drug target validation. Moreover, siRNAs are potentially useful as therapeutic agents against: (1) diseases that are caused by over-expression or misexpression of genes; and (2) diseases brought about by expression of genes that contain mutations.

Successful siRNA-dependent gene silencing depends on a number of factors. One of the most contentious issues in RNAi is the question of the necessity of siRNA design, i.e., considering the sequence of the siRNA used. Early work in C. elegans and plants circumvented the issue of design by introducing long dsRNA (see, for instance, Fire, A. et al. (1998) Nature 391:806-811). In this primitive organism, long dsRNA molecules are cleaved into siRNA by Dicer, thus generating a diverse population of duplexes that can potentially cover the entire transcript. While some fraction of these molecules are non-functional (i.e., induce little or no silencing) one or more have the potential to be highly functional, thereby silencing the gene of interest and alleviating the need for siRNA design. Unfortunately, due to the interferon response, this same approach is unavailable for mammalian systems. While this effect can be circumvented by bypassing the Dicer cleavage step and directly introducing siRNA, this tactic carries with it the risk that the chosen siRNA sequence may be non-functional or semi-functional.

A number of researches have expressed the view that siRNA design is not a crucial element of RNAi. On the other hand, others in the field have begun to explore the possibility that RNAi can be made more efficient by paying attention to the design of the siRNA. Unfortunately, none of the reported methods have provided a satisfactory scheme for reliably selecting siRNA with acceptable levels of functionality. Accordingly, there is a need to develop rational criteria by which to select siRNA with an acceptable level of functionality, and to identify siRNA that have this improved level of functionality, as well as to identify siRNAs that are hyperfunctional.

SUMMARY OF THE INVENTION

The present invention is directed to increasing the efficiency of RNAi, particularly in mammalian systems. Accordingly, the present invention provides kits, siRNAs and methods for increasing siRNA efficacy.

According to a first embodiment, the present invention provides a kit for gene silencing, wherein said kit is comprised of a pool of at least two siRNA duplexes, each of which is comprised of a sequence that is complementary to a portion of the sequence of one or more target messenger RNA, and each of which is selected using non-target specific criteria.

According to a second embodiment, the present invention provides a method for selecting an siRNA, said method comprising applying selection criteria to a set of potential siRNA that comprise 18-30 base pairs, wherein said selection criteria are non-target specific criteria, and said set comprises at least two siRNAs and each of said at least two siRNAs contains a sequence that is at least substantially complementary to a target gene; and determining the relative functionality of the at least two siRNAs.

According to a third embodiment, the present invention also provides a method for selecting an siRNA wherein said selection criteria are embodied in a formula comprising: (−14)*G₁₃−13*A₁−12*U₇−11*U₂−10*A₁₁−10*U₄−10*C₃−10*C₅−10*C₆−9*A₁₀−9*U₉−9*C₁₈−8*G₁₀−7*U₁−7*U₁₆−7*C₁₇−7*C₁₉+7*U₁₇+8*A₂+8*A₄+8*A₅+8*C₄+9*G₈+10*A₇+10*U₁₈+11*A₁₉+11*C₉+15*G₁+18*A₃+19*U₁₀−Tm−3*(GC_(total))−6*(GC₁₅₋₁₉)−30*X; or  Formula VIII (−8)*A1+(−1)*A2+(12)*A3+(7)*A4+(18)*A5+(12)*A6+(19)*A7+(6)*A8+(−4)*A9+(−5)*A10+(−2)*A11+(−5)*A12+(17)*A13+(−3)*A14+(4)*A15+(2)*A16+(8)*A17+(11)*A18+(30)*A19+(−13)*U1+(−10)*U2+(2)*U3+(−2)*U4+(−5)*U5+(5)*U6+(−2)*U7+(−10)*U8+(−5)*U9+(15)*U10+(−1)*U11+(0)*U12+(10)*U13+(−9)*U14+(−13)*U15+(−10)*U16+(3)*U17+(9)*U18+(9)*U19+(7)*C1+(3)*C2+(−21)*C3+(5)*C4+(−9)*C5+(−20)*C6+(−18)*C7+(−5)*C8+(5)*C9+(1)*C10+(2)*C11+(−5)*C12+(−3)*C13+(−6)*C14+(−2)*C15+(−5)*C16+(−3)*C17+(−12)*C18+(−18)*C19+(14)*G1+(8)*G2+(7)*G3+(−10)*G4+(−4)*G5+(2)*G6+(1)*G7+(9)*G8+(5)*G9+(−11)*G10+(1)*G11+(9)*G12+(−24)*G13+(18)*G14+(11)*G15+(13)*G16+(−7)*G17+(−9)*G18+(−22)*G19+6*(number of A+U in position 15-19)-3*(number of G+C in whole siRNA),  Formula X wherein position numbering begins at the 5′-most position of a sense strand, and A₁=1 if A is the base at position 1 of the sense strand, otherwise its value is 0; A₂=1 if A is the base at position 2 of the sense strand, otherwise its value is 0; A₃=1 if A is the base at position 3 of the sense strand, otherwise its value is 0; A₄=1 if A is the base at position 4 of the sense strand, otherwise its value is 0; A₅=1 if A is the base at position 5 of the sense strand, otherwise its value is 0; A₆=1 if A is the base at position 6 of the sense strand, otherwise its value is 0; A₇=1 if A is the base at position 7 of the sense strand, otherwise its value is 0; A₁₀=1 if A is the base at position 10 of the sense strand, otherwise its value is 0; A₁₁=1 if A is the base at position 11 of the sense strand, otherwise its value is 0; A₁₃=1 if A is the base at position 13 of the sense strand, otherwise its value is 0; A₁₉=1 if A is the base at position 19 of the sense strand, otherwise if another base is present or the sense strand is only 18 base pairs in length, its value is 0; C₃=1 if C is the base at position 3 of the sense strand, otherwise its value is 0; C₄=1 if C is the base at position 4 of the sense strand, otherwise its value is 0; C₅=1 if C is the base at position 5 of the sense strand, otherwise its value is 0; C₆=1 if C is the base at position 6 of the sense strand, otherwise its value is 0; C₇=1 if C is the base at position 7 of the sense strand, otherwise its value is 0; C₉=1 if C is the base at position 9 of the sense strand, otherwise its value is 0; C₁₇=1 if C is the base at position 17 of the sense strand, otherwise its value is 0; C₁₈=1 if C is the base at position 18 of the sense strand, otherwise its value is 0; C₁₉=1 if C is the base at position 19 of the sense strand, otherwise if another base is present or the sense strand is only 18 base pairs in length, its value is 0; G₁=1 if G is the base at position 1 on the sense strand, otherwise its value is 0; G₂=1 if G is the base at position 2 of the sense strand, otherwise its value is 0; G₈=1 if G is the base at position 8 on the sense strand, otherwise its value is 0; G₁₀=1 if G is the base at position 10 on the sense strand, otherwise its value is 0; G₁₃=1 if G is the base at position 13 on the sense strand, otherwise its value is 0; G₁₉=1 if G is the base at position 19 of the sense strand, otherwise if another base is present or the sense strand is only 18 base pairs in length, its value is 0; U₁=1 if U is the base at position 1 on the sense strand, otherwise its value is 0; U₂=1 if U is the base at position 2 on the sense strand, otherwise its value is 0; U₃=1 if U is the base at position 3 on the sense strand, otherwise its value is 0; U₄=1 if U is the base at position 4 on the sense strand, otherwise its value is 0; U₇=1 if U is the base at position 7 on the sense strand, otherwise its value is 0; U₉=1 if U is the base at position 9 on the sense strand, otherwise its value is 0; U₁₀=1 if U is the base at position 10 on the sense strand, otherwise its value is 0; U₁₅=1 if U is the base at position 15 on the sense strand, otherwise its value is 0; U₁₆=1 if U is the base at position 16 on the sense strand, otherwise its value is 0; U₁₇=1 if U is the base at position 17 on the sense strand, otherwise its value is 0; U₁₈=1 if U is the base at position 18 on the sense strand, otherwise its value is 0. GC₅₋₁₉=the number of G and C bases within positions 15-19 of the sense strand, or within positions 15-18 if the sense strand is only 18 base pairs in length; GC_(total)=the number of G and C bases in the sense strand; Tm=100 if the siRNA oligo has the internal repeat longer then 4 base pairs, otherwise its value is 0; and X=the number of times that the same nucleotide repeats four or more times in a row.

According to a fourth embodiment, the invention provides a method for developing an algorithm for selecting siRNA, said method comprising: (a) selecting a set of siRNA; (b) measuring gene silencing ability of each siRNA from said set; (c) determining relative functionality of each siRNA; (d) determining improved functionality by the presence or absence of at least one variable selected from the group consisting of the presence or absence of a particular nucleotide at a particular position, the total number of As and Us in positions 15-19, the number of times that the same nucleotide repeats within a given sequence, and the total number of Gs and Cs; and (e) developing an algorithm using the information of step (d).

According to a fifth embodiment, the present invention provides a kit, wherein said kit is comprised of at least two siRNAs, wherein said at least two siRNAs comprise a first optimized siRNA and a second optimized siRNA, wherein said first optimized siRNA and said second optimized siRNA are optimized according a formula comprising Formula X.

The present invention also provides a method for identifying a hyperfunctional siRNA, comprising applying selection criteria to a set of potential siRNA that comprise 18-30 base pairs, wherein said selection criteria are non-target specific criteria, and said set comprises at least two siRNAs and each of said at least two siRNAs contains a sequence that is at least substantially complementary to a target gene; determining the relative functionality of the at least two siRNAs and assigning each of the at least two siRNAs a functionality score; and selecting siRNAs from the at least two siRNAs that have a functionality score that reflects greater than 80 percent silencing at a concentration in the picomolar range, wherein said greater than 80 percent silencing endures for greater than 120 hours.

According to a sixth embodiment, the present invention provides a hyperfunctional siRNA that is capable of silencing Bcl2.

According to a seventh embodiment, the present invention provides a method for developing an siRNA algorithm for selecting functional and hyperfunctional siRNAs for a given sequence. The method comprises:

(a) selecting a set of siRNAs;

(b) measuring the gene silencing ability of each siRNA from said set;

(c) determining the relative functionality of each siRNA;

(d) determining the amount of improved functionality by the presence or absence of at least one variable selected from the group consisting of the total GC content, melting temperature of the siRNA, GC content at positions 15-19, the presence or absence of a particular nucleotide at a particular position, relative thermodynamic stability at particular positions in a duplex, and the number of times that the same nucleotide repeats within a given sequence; and

(e) developing an algorithm using the information of step (d).

According to this embodiment, preferably the set of siRNAs comprises at least 90 siRNAs from at least one gene, more preferably at least 180 siRNAs from at least two different genes, and most preferably at least 270 and 360 siRNAs from at least three and four different genes, respectively. Additionally, in step (d) the determination is made with preferably at least two, more preferably at least three, even more preferably at least four, and most preferably all of the variables. The resulting algorithm is not target sequence specific.

In another embodiment, the present invention provides rationally designed siRNAs identified using the formulas above.

In yet another embodiment, the present invention is directed to hyperfunctional siRNA.

The ability to use the above algorithms, which are not sequence or species specific, allows for the cost-effective selection of optimized siRNAs for specific target sequences. Accordingly, there will be both greater efficiency and reliability in the use of siRNA technologies.

In various embodiments, siRNAs that target nucleotide sequences for deubiquitination enzymes are provided. In various embodiments, the siRNAs are rationally designed. In various embodiments, the siRNAs are functional or hyperfunctional.

In various embodiments, an siRNA that targets nucleotide sequence for a deubiquitination enzyme is provided, wherein the siRNA is selected from the group consisting of various siRNA sequences targeting nucleotide sequences for deubiquitination enzymes that are disclosed herein. In various embodiments, the siRNA sequence is selected from the group consisting of SEQ ID NO. 438 to SEQ ID NO. 3940.

In various embodiments, siRNA comprising a sense region and an antisense region are provided, said sense region and said antisense region together form a duplex region comprising 18-30 base pairs, and said sense region comprises a sequence that is at least 90% similar to a sequence selected from the group consisting of siRNA sequences targeting nucleotide sequences for deubiquitination enzymes that are disclosed herein. In various embodiments, the siRNA sequence is selected from the group consisting of SEQ ID NO. 438 to SEQ ID NO. 3940.

In various embodiments, an siRNA comprising a sense region and an antisense region is provided, said sense region and said antisense region together form a duplex region comprising 18-30 base pairs, and said sense region comprises a sequence that is identical to a contiguous stretch of at least 18 bases of a sequence selected from the group consisting of SEQ ID NO. 438 to SEQ ID NO. 3940. In various embodiments, the duplex region is 19-30 base pairs, and the sense region comprises a sequence that is identical to a sequence selected from the group consisting of SEQ ID NO. 438 to SEQ ID NO. 3940.

In various embodiments, a pool of at least two siRNAs is provided, wherein said pool comprises a first siRNA and a second siRNA, said first siRNA comprising a duplex region of length 18-30 base pairs that has a first sense region that is at least 90% similar to 18 bases of a first sequence selected from the group consisting of SEQ ID NO. 438 to SEQ ID NO. 3940, and said second siRNA comprises a duplex region of length 18-30 base pairs that has a second sense region that is at least 90% similar to 18 bases of a second sequence selected from the group consisting of SEQ ID NO. 438 to SEQ ID NO. 3940, wherein said first sense region and said second sense region are not identical.

In various embodiments, the first sense region comprises a sequence that is identical to at least 18 bases of a sequence selected from the group consisting of SEQ ID NO. 438 to SEQ ID NO. 3940, and said second sense region comprises a sequence that is identical to at least 18 bases of a sequence selected from the group consisting of SEQ ID NO. 438 to SEQ ID NO. 3940. In various embodiments, the duplex of said first siRNA is 19-30 base pairs, and said first sense region comprises a sequence that is at least 90% similar to a sequence selected from the group consisting of SEQ ID NO. 438 to SEQ ID NO. 3940, and said duplex of said second siRNA is 19-30 base pairs and comprises a sequence that is at least 90% similar to a sequence selected from the group consisting of SEQ ID NO. 438 to SEQ ID NO. 3940.

In various embodiments, the duplex of said first siRNA is 19-30 base pairs and said first sense region comprises a sequence that is identical to at least 18 bases of a sequence selected from the group consisting of SEQ ID NO. 438 to SEQ ID NO. 3940, and said duplex of said second siRNA is 19-30 base pairs and said second region comprises a sequence that is identical to a sequence selected from the group consisting of SEQ ID NO. 438 to SEQ ID NO. 3940.

For a better understanding of the present invention together with other and further advantages and embodiments, reference is made to the following description taken in conjunction with the examples, the scope of which is set forth in the appended claims.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows a model for siRNA-RISC interactions. RISC has the ability to interact with either end of the siRNA or miRNA molecule. Following binding, the duplex is unwound, and the relevant target is identified, cleaved, and released.

FIG. 2 is a representation of the functionality of two hundred and seventy siRNA duplexes that were generated to target human cyclophilin, human diazepam-binding inhibitor (DB), and firefly luciferase.

FIG. 3 a is a representation of the silencing effect of 30 siRNAs in three different cells lines, HEK293, DU145, and Hela. FIG. 3 b shows the frequency of different functional groups (>95% silencing (black), >80% silencing (gray), >50% silencing (dark gray), and <50% silencing (white)) based on GC content. In cases where a given bar is absent from a particular GC percentage, no siRNA were identified for that particular group. FIG. 3 c shows the frequency of different functional groups based on melting temperature (Tm).

FIG. 4 is a representation of a statistical analysis that revealed correlations between silencing and five sequence-related properties of siRNA: (A) an A at position 19 of the sense strand, (B) an A at position 3 of the sense strand, (C) a U at position 10 of the sense strand, (D) a base other than G at position 13 of the sense strand, and (E) a base other than C at position 19 of the sense strand. All variables were correlated with siRNA silencing of firefly luciferase and human cyclophilin. siRNAs satisfying the criterion are grouped on the left (Selected) while those that do not, are grouped on the right (Eliminated). Y-axis is “% Silencing of Control.” Each position on the X-axis represents a unique siRNA.

FIGS. 5A and 5B are representations of firefly luciferase and cyclophilin siRNA panels sorted according to functionality and predicted values using Formula VIII. The siRNA found within the circle represent those that have Formula VIII values (SMARTSCORES™, or siRNA rank) above zero. siRNA outside the indicated area have calculated Formula VIII values that are below zero. Y-axis is “Expression (% Control).” Each position on the X-axis represents a unique siRNA.

FIG. 6A is a representation of the average internal stability profile (AISP) derived from 270 siRNAs taken from three separate genes (cyclophilin B, DBI and firefly luciferase). Graphs represent AISP values of highly functional, functional, and non-functional siRNA. FIG. 6B is a comparison between the AISP of naturally derived GFP siRNA (filled squares) and the AISP of siRNA from cyclophilin B, DBI, and luciferase having >90% silencing properties (no fill) for the antisense strand. “DG” is the symbol for ΔG, free energy.

FIG. 7 is a histogram showing the differences in duplex functionality upon introduction of base pair mismatches. The X-axis shows the mismatch introduced in the siRNA and the position it is introduced (e.g., 8C>A reveals that position 8 (which normally has a C) has been changed to an A). The Y-axis is “% Silencing (Normalized to Control).” The samples on the X-axis represent siRNAs at 100 nM and are, reading from left to right: 1A to C, 1A to G, 1A to U; 2A to C, 2A to G, 2A to U; 3A to C, 3A to G, 3A to U; 4G to A, 4G to C; 4G to U; 5U to A, 5U to C, 5U to G; 6U to A, 6U to C, 6U to G; 7G to A, 7G to C, 7G to U; 8C to A, 8C to G, 8C to U; 9G to A, 9G to C, 9G to U; 10C to A, 10C to G, 10C to U; 11G to A, 11G to C, 11G to U; 12G to A, 12G to C, 12G to U; 13A to C, 13A to G, 13A to U; 14G to A, 14G to C, 14G to U; 15G to A, 15G to C, 15G to U; 16A to C, 16A to G, 16A to U; 17G to A, 17G to C, 17G to U; 18U to A, 18U to C, 18U to G; 19U to A, 19U to C, 19U to G; 20 wt; Control.

FIG. 8 is histogram that shows the effects of 5′sense and antisense strand modification with 2′-O-methylation on functionality.

FIG. 9 shows a graph of SMARTSCORES™, or siRNA rank, versus RNAi silencing values for more than 360 siRNA directed against 30 different genes. SiRNA to the right of the vertical bar represent those siRNA that have desirable SMARTSCORES™, or siRNA rank.

FIGS. 10A-E compare the RNAi of five different genes (SEAP, DBI, PLK, Firefly Luciferase, and Renilla Luciferase) by varying numbers of randomly selected siRNA and four rationally designed (SMART-selected) siRNA chosen using the algorithm described in Formula VIII. In addition, RNAi induced by a pool of the four SMART-selected siRNA is reported at two different concentrations (100 and 400 nM). 10F is a comparison between a pool of randomly selected EGFR siRNA (Pool 1) and a pool of SMART-selected EGFR siRNA (Pool 2). Pool 1, S1-S4 and Pool 2 S1-S4 represent the individual members that made up each respective pool. Note that numbers for random siRNAs represent the position of the 5′ end of the sense strand of the duplex. The Y-axis represents the % expression of the control(s). The X-axis is the percent expression of the control.

FIG. 11 shows the Western blot results from cells treated with siRNA directed against twelve different genes involved in the clathrin-dependent endocytosis pathway (CHC, DynII, CALM, CLCa, CLCb, Eps15, Eps15R, Rab5a, Rab5b, Rab5c, P2 subunit of AP-2 and EEA.1). siRNA were selected using Formula VIII. “Pool” represents a mixture of duplexes 1-4. Total concentration of each siRNA in the pool is 25 nM. Total concentration=4×25=100 nM.

FIG. 12 is a representation of the gene silencing capabilities of rationally-selected siRNA directed against ten different genes (human and mouse cyclophilin, C-myc, human lamin A/C, QB (ubiquinol-cytochrome c reductase core protein I), MEK1 and MEK2, ATE1 (arginyl-tRNA protein transferase), GAPDH, and Eg5). The Y-axis is the percent expression of the control. Numbers 1, 2, 3 and 4 represent individual rationally selected siRNA. “Pool” represents a mixture of the four individual siRNA.

FIG. 13 is the sequence of the top ten Bcl2 siRNAs as determined by Formula VIII. Sequences are listed 5′ to 3′.

FIG. 14 is the knockdown by the top ten Bcl2 siRNAs at 100 nM concentrations. The Y-axis represents the amount of expression relative to the non-specific (ns) and transfection mixture control.

FIG. 15 represents a functional walk where siRNA beginning on every other base pair of a region of the luciferase gene are tested for the ability to silence the luciferase gene. The Y-axis represents the percent expression relative to a control. The X-axis represents the position of each individual siRNA. Reading from left to right across the X-axis, the position designations are 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, and Plasmid.

FIGS. 16A and 16B are histograms demonstrating the inhibition of target gene expression by pools of 2 (16A) and 3 (16B) siRNA duplexes taken from the walk described in FIG. 15. The Y-axis in each represents the percent expression relative to control. The X-axis in each represents the position of the first siRNA in paired pools, or trios of siRNAs. For instance, the first paired pool contains siRNAs 1 and 3. The second paired pool contains siRNAs 3 and 5. Pool 3 (of paired pools) contains siRNAs 5 and 7, and so on. For each of 16A and 16B, the X-axis from left to right reads 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, and Plasmid.

FIGS. 17A and 17B are histograms demonstrating the inhibition of target gene expression by pools of 4 (17A) and 5 (17B) siRNA duplexes. The Y-axis in each represents the percent expression relative to control. The X-axis in each represents the position of the first siRNA in each pool. For each of 17A and 17B, the X-axis from left to right reads 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, and Plasmid.

FIGS. 18A and 18B are histograms demonstrating the inhibition of target gene expression by siRNAs that are ten (18A) and twenty (18B) base pairs base pairs apart. The Y-axis represents the percent expression relative to a control. The X-axis represents the position of the first siRNA in each pool. For each of 18A and 18B, the X-axis from left to right reads 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, and Plasmid.

FIG. 19 shows that pools of siRNAs (dark gray bar) work as well (or better) than the best siRNA in the pool (light gray bar). The Y-axis represents the percent expression relative to a control. The X-axis represents the position of the first siRNA in each pool. The X-axis from left to right reads 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, and Plasmid.

FIG. 20 shows that the combination of several semifunctional siRNAs (dark gray) result in a significant improvement of gene expression inhibition over individual (semi-functional; light gray) siRNA. The Y-axis represents the percent expression relative to a control.

FIGS. 21A, 21B and 21C show both pools (Library, Lib) and individual siRNAs in inhibition of gene expression of Beta-Galactosidase, Renilla Luciferase and SEAP (alkaline phosphatase). Numbers on the X-axis indicate the position of the 5′-most nucleotide of the sense strand of the duplex. The Y-axis represents the percent expression of each gene relative to a control. Libraries contain 19 nucleotide long siRNAs (not including overhangs) that begin at the following nucleotides: SEAP: Lib 1: 206, 766, 812, 923, Lib 2: 1117, 1280, 1300, 1487, Lib 3: 206, 766, 812, 923, 1117, 1280, 1300, 1487, Lib 4: 206, 812, 1117, 1300, Lib 5: 766, 923, 1280, 1487, Lib 6: 206, 1487; Bgal: Lib 1: 979, 1339, 2029, 2590, Lib 2: 1087, 1783, 2399, 3257, Lib 3: 979, 1783, 2590, 3257, Lib 4: 979, 1087, 1339, 1783, 2029, 2399, 2590, 3257, Lib 5: 979, 1087, 1339, 1783, Lib 6: 2029, 2399, 2590, 3257; Renilla: Lib 1: 174, 300, 432, 568, Lib 2: 592, 633, 729, 867, Lib 3: 174, 300, 432, 568, 592, 633, 729, 867, Lib 4: 174, 432, 592, 729, Lib 5: 300, 568, 633, 867, Lib 6: 592, 568.

FIG. 22 shows the results of an EGFR and TfnR internalization assay when single gene knockdowns are performed. The Y-axis represents percent internalization relative to control.

FIG. 23 shows the results of an EGFR and TfnR internalization assay when multiple genes are knocked down (e.g., Rab5a, b, c). The Y-axis represents the percent internalization relative to control.

FIG. 24 shows the simultaneous knockdown of four different genes. siRNAs directed against G6PD, GAPDH, PLK, and UQC were simultaneously introduced into cells. Twenty-four hours later, cultures were harvested and assayed for mRNA target levels for each of the four genes. A comparison is made between cells transfected with individual siRNAs vs. a pool of siRNAs directed against all four genes.

FIG. 25 shows the functionality of ten siRNAs at 0.3 nM concentrations.

DETAILED DESCRIPTION Definitions

Unless stated otherwise, the following terms and phrases have the meanings provided below:

Complementary

The term “complementary” refers to the ability of polynucleotides to form base pairs with one another. Base pairs are typically formed by hydrogen bonds between nucleotide units in antiparallel polynucleotide strands. Complementary polynucleotide strands can base pair in the Watson-Crick manner (e.g., A to T, A to U, C to G), or in any other manner that allows for the formation of duplexes. As persons skilled in the art are aware, when using RNA as opposed to DNA, uracil rather than thymine is the base that is considered to be complementary to adenosine. However, when a U is denoted in the context of the present invention, the ability to substitute a T is implied, unless otherwise stated.

Perfect complementarity or 100% complementarity refers to the situation in which each nucleotide unit of one polynucleotide strand can hydrogen bond with a nucleotide unit of a second polynucleotide strand. Less than perfect complementarity refers to the situation in which some, but not all, nucleotide units of two strands can hydrogen bond with each other. For example, for two 20-mers, if only two base pairs on each strand can hydrogen bond with each other, the polynucleotide strands exhibit 10% complementarity. In the same example, if 18 base pairs on each strand can hydrogen bond with each other, the polynucleotide strands exhibit 90% complementarity.

Deoxynucleotide

The term “deoxynucleotide” refers to a nucleotide or polynucleotide lacking a hydroxyl group (OH group) at the 2′ and/or 3′ position of a sugar moiety. Instead, it has a hydrogen bonded to the 2′ and/or 3′ carbon. Within an RNA molecule that comprises one or more deoxynucleotides, “deoxynucleotide” refers to the lack of an OH group at the 2′ position of the sugar moiety, having instead a hydrogen bonded directly to the 2′ carbon.

Deoxyribonucleotide

The terms “deoxyribonucleotide” and “DNA” refer to a nucleotide or polynucleotide comprising at least one sugar moiety that has an H, rather than an OH, at its 2′ and/or 3′position.

Duplex Region

The phrase “duplex region” refers to the region in two complementary or substantially complementary polynucleotides that form base pairs with one another, either by Watson-Crick base pairing or any other manner that allows for a stabilized duplex between polynucleotide strands that are complementary or substantially complementary. For example, a polynucleotide strand having 21 nucleotide units can base pair with another polynucleotide of 21 nucleotide units, yet only 19 bases on each strand are complementary or substantially complementary, such that the “duplex region” has 19 base pairs. The remaining bases may, for example, exist as 5′ and 3′ overhangs. Further, within the duplex region, 100% complementarity is not required; substantial complementarity is allowable within a duplex region. Substantial complementarity refers to 79% or greater complementarity. For example, a mismatch in a duplex region consisting of 19 base pairs results in 94.7% complementarity, rendering the duplex region substantially complementary.

Filters

The term “filter” refers to one or more procedures that are performed on sequences that are identified by the algorithm. In some instances, filtering includes in silico procedures where sequences identified by the algorithm can be screened to identify duplexes carrying desirable or undesirable motifs. Sequences carrying such motifs can be selected for, or selected against, to obtain a final set with the preferred properties. In other instances, filtering includes wet lab experiments. For instance, sequences identified by one or more versions of the algorithm can be screened using any one of a number of procedures to identify duplexes that have hyperfunctional traits (e.g., they exhibit a high degree of silencing at subnanomolar concentrations and/or exhibit high degrees of silencing longevity).

Gene Silencing

The phrase “gene silencing” refers to a process by which the expression of a specific gene product is lessened or attenuated. Gene silencing can take place by a variety of pathways. Unless specified otherwise, as used herein, gene silencing refers to decreases in gene product expression that results from RNA interference (RNAi), a defined, though partially characterized pathway whereby small inhibitory RNA (siRNA) act in concert with host proteins (e.g., the RNA induced silencing complex, RISC) to degrade messenger RNA (mRNA) in a sequence-dependent fashion. The level of gene silencing can be measured by a variety of means, including, but not limited to, measurement of transcript levels by Northern Blot Analysis, B-DNA techniques, transcription-sensitive reporter constructs, expression profiling (e.g., DNA chips), and related technologies. Alternatively, the level of silencing can be measured by assessing the level of the protein encoded by a specific gene. This can be accomplished by performing a number of studies including Western Analysis, measuring the levels of expression of a reporter protein that has e.g., fluorescent properties (e.g., GFP) or enzymatic activity (e.g., alkaline phosphatases), or several other procedures.

miRNA

The term “miRNA” refers to microRNA.

Nucleotide

The term “nucleotide” refers to a ribonucleotide or a deoxyribonucleotide or modified form thereof, as well as an analog thereof. Nucleotides include species that comprise purines, e.g., adenine, hypoxanthine, guanine, and their derivatives and analogs, as well as pyrimidines, e.g., cytosine, uracil, thymine, and their derivatives and analogs.

Nucleotide analogs include nucleotides having modifications in the chemical structure of the base, sugar and/or phosphate, including, but not limited to, 5-position pyrimidine modifications, 8-position purine modifications, modifications at cytosine exocyclic amines, and substitution of 5-bromo-uracil; and 2′-position sugar modifications, including but not limited to, sugar-modified ribonucleotides in which the 2′-OH is replaced by a group such as an H, OR, R, halo, SH, SR, NH₂, NHR, NR₂, or CN, wherein R is an alkyl moiety. Nucleotide analogs are also meant to include nucleotides with bases such as inosine, queuosine, xanthine, sugars such as 2′-methyl ribose, non-natural phosphodiester linkages such as methylphosphonates, phosphorothioates and peptides.

Modified bases refer to nucleotide bases such as, for example, adenine, guanine, cytosine, thymine, uracil, xanthine, inosine, and queuosine that have been modified by the replacement or addition of one or more atoms or groups. Some examples of types of modifications that can comprise nucleotides that are modified with respect to the base moieties include but are not limited to, alkylated, halogenated, thiolated, aminated, amidated, or acetylated bases, individually or in combination. More specific examples include, for example, 5-propynyluridine, 5-propynylcytidine, 6-methyladenine, 6-methylguanine, N,N,-dimethyladenine, 2-propyladenine, 2-propylguanine, 2-aminoadenine, 1-methylinosine, 3-methyluridine, 5-methylcytidine, 5-methyluridine and other nucleotides having a modification at the 5 position, 5-(2-amino)propyl uridine, 5-halocytidine, 5-halouridine, 4-acetylcytidine, 1-methyladenosine, 2-methyladenosine, 3-methylcytidine, 6-methyluridine, 2-methylguanosine, 7-methylguanosine, 2,2-dimethylguanosine, 5-methylaminoethyluridine, 5-methyloxyuridine, deazanucleotides such as 7-deaza-adenosine, 6-azouridine, 6-azocytidine, 6-azothymidine, 5-methyl-2-thiouridine, other thio bases such as 2-thiouridine and 4-thiouridine and 2-thiocytidine, dihydrouridine, pseudouridine, queuosine, archaeosine, naphthyl and substituted naphthyl groups, any O- and N-alkylated purines and pyrimidines such as N6-methyladenosine, 5-methylcarbonylmethyluridine, uridine 5-oxyacetic acid, pyridine-4-one, pyridine-2-one, phenyl and modified phenyl groups such as aminophenol or 2,4,6-trimethoxy benzene, modified cytosines that act as G-clamp nucleotides, 8-substituted adenines and guanines, 5-substituted uracils and thymines, azapyrimidines, carboxyhydroxyalkyl nucleotides, carboxyalkylaminoalkyl nucleotides, and alkylcarbonylalkylated nucleotides. Modified nucleotides also include those nucleotides that are modified with respect to the sugar moiety, as well as nucleotides having sugars or analogs thereof that are not ribosyl. For example, the sugar moieties may be, or be based on, mannoses, arabinoses, glucopyranoses, galactopyranoses, 4′-thioribose, and other sugars, heterocycles, or carbocycles.

The term nucleotide is also meant to include what are known in the art as universal bases. By way of example, universal bases include but are not limited to 3-nitropyrrole, 5-nitroindole, or nebularine. The term “nucleotide” is also meant to include the N3′ to P5′ phosphoramidate, resulting from the substitution of a ribosyl 3′ oxygen with an amine group.

Further, the term nucleotide also includes those species that have a detectable label, such as for example a radioactive or fluorescent moiety, or mass label attached to the nucleotide.

Off-Target Silencing and Off-Target Interference

The phrases “off-target silencing” and “off-target interference” are defined as degradation of mRNA other than the intended target mRNA due to overlapping and/or partial homology with secondary mRNA messages.

Polynucleotide

The term “polynucleotide” refers to polymers of nucleotides, and includes but is not limited to DNA, RNA, DNA/RNA hybrids including polynucleotide chains of regularly and/or irregularly alternating deoxyribosyl moieties and ribosyl moieties (i.e., wherein alternate nucleotide units have an —OH, then and —H, then an —OH, then an —H, and so on at the 2′ position of a sugar moiety), and modifications of these kinds of polynucleotides, wherein the attachment of various entities or moieties to the nucleotide units at any position are included.

Polyribonucleotide

The term “polyribonucleotide” refers to a polynucleotide comprising two or more modified or unmodified ribonucleotides and/or their analogs. The term “polyribonucleotide” is used interchangeably with the term “oligoribonucleotide.”

Ribonucleotide and Ribonucleic Acid

The term “ribonucleotide” and the phrase “ribonucleic acid” (RNA), refer to a modified or unmodified nucleotide or polynucleotide comprising at least one ribonucleotide unit. A ribonucleotide unit comprises an hydroxyl group attached to the 2′ position of a ribosyl moiety that has a nitrogenous base attached in N-glycosidic linkage at the 1′ position of a ribosyl moiety, and a moiety that either allows for linkage to another nucleotide or precludes linkage.

siRNA

The term “siRNA” refers to small inhibitory RNA duplexes that induce the RNA interference (RNAi) pathway. These molecules can vary in length (generally 18-30 base pairs) and contain varying degrees of complementarity to their target mRNA in the antisense strand. Some, but not all, siRNA have unpaired overhanging bases on the 5′ or 3′ end of the sense strand and/or the antisense strand. The term “siRNA” includes duplexes of two separate strands, as well as single strands that can form hairpin structures comprising a duplex region.

siRNA may be divided into five (5) groups (non-functional, semi-functional, functional, highly functional, and hyper-functional) based on the level or degree of silencing that they induce in cultured cell lines. As used herein, these definitions are based on a set of conditions where the siRNA is transfected into said cell line at a concentration of 100 nM and the level of silencing is tested at a time of roughly 24 hours after transfection, and not exceeding 72 hours after transfection. In this context, “non-functional siRNA” are defined as those siRNA that induce less than 50% (<50%) target silencing. “Semi-functional siRNA” induce 50-79% target silencing. “Functional siRNA” are molecules that induce 80-95% gene silencing. “Highly-functional siRNA” are molecules that induce greater than 95% gene silencing. “Hyperfunctional siRNA” are a special class of molecules. For purposes of this document, hyperfunctional siRNA are defined as those molecules that: (1) induce greater than 95% silencing of a specific target when they are transfected at subnanomolar concentrations (i.e., less than one nanomolar); and/or (2) induce functional (or better) levels of silencing for greater than 96 hours. These relative functionalities (though not intended to be absolutes) may be used to compare siRNAs to a particular target for applications such as functional genomics, target identification and therapeutics.

SMARTSCORE™, or siRNA rank

The term “SMARTSCORE™”, or “siRNA rank” refers to a number determined by applying any of the formulas to a given siRNA sequence. The term “SMART-selected” or “rationally selected” or “rational selection” refers to siRNA that have been selected on the basis of their SMARTSCORES™, or siRNA ranking.

Substantially Similar

The phrase “substantially similar” refers to a similarity of at least 90% with respect to the identity of the bases of the sequence.

Target

The term “target” is used in a variety of different forms throughout this document and is defined by the context in which it is used. “Target mRNA” refers to a messenger RNA to which a given siRNA can be directed against. “Target sequence” and “target site” refer to a sequence within the mRNA to which the sense strand of an siRNA shows varying degrees of homology and the antisense strand exhibits varying degrees of complementarity. The phrase “siRNA target” can refer to the gene, mRNA, or protein against which an siRNA is directed. Similarly, “target silencing” can refer to the state of a gene, or the corresponding mRNA or protein.

Transfection

The term “transfection” refers to a process by which agents are introduced into a cell. The list of agents that can be transfected is large and includes, but is not limited to, siRNA, sense and/or anti-sense sequences, DNA encoding one or more genes and organized into an expression plasmid, proteins, protein fragments, and more. There are multiple methods for transfecting agents into a cell including, but not limited to, electroporation, calcium phosphate-based transfections, DEAE-dextran-based transfections, lipid-based transfections, molecular conjugate-based transfections (e.g., polylysine-DNA conjugates), microinjection and others.

The present invention is directed to improving the efficiency of gene silencing by siRNA. Through the inclusion of multiple siRNA sequences that are targeted to a particular gene and/or selecting an siRNA sequence based on certain defined criteria, improved efficiency may be achieved.

The present invention will now be described in connection with preferred embodiments. These embodiments are presented in order to aid in an understanding of the present invention and are not intended, and should not be construed, to limit the invention in any way. All alternatives, modifications and equivalents that may become apparent to those of ordinary skill upon reading this disclosure are included within the spirit and scope of the present invention.

Furthermore, this disclosure is not a primer on RNA interference. Basic concepts known to persons skilled in the art have not been set forth in detail.

The present invention is directed to increasing the efficiency of RNAi, particularly in mammalian systems. Accordingly, the present invention provides kits, siRNAs and methods for increasing siRNA efficacy.

According to a first embodiment, the present invention provides a kit for gene silencing, wherein said kit is comprised of a pool of at least two siRNA duplexes, each of which is comprised of a sequence that is complementary to a portion of the sequence of one or more target messenger RNA, and each of which is selected using non-target specific criteria. Each of the at least two siRNA duplexes of the kit complementary to a portion of the sequence of one or more target mRNAs is preferably selected using Formula X.

According to a second embodiment, the present invention provides a method for selecting an siRNA, said method comprising applying selection criteria to a set of potential siRNA that comprise 18-30 base pairs, wherein said selection criteria are non-target specific criteria, and said set comprises at least two siRNAs and each of said at least two siRNAs contains a sequence that is at least substantially complementary to a target gene; and determining the relative functionality of the at least two siRNAs.

In one embodiment, the present invention also provides a method wherein said selection criteria are embodied in a formula comprising: (−14)*G₁₃−13*A₁−12*U₇−11*U₂−10*A₁₁−10*U₄−10*C₃−10*C₅−1*C₆−9*A₁₀−9*U₉−9*C₁₈−8*G₁₀−7*U₁−7*U₁₆−7*C₁₇−7*C₁₉+7*U₁₇+8*A₂+8*A₄+8*A₅+8*C₄+9*G₈+10*A₇+10*U₁₈+11*A₁₉+11*C₉+15*G₁+18*A₃+19*U₁₀−Tm−3*(GC_(total))−6*(GC₁₅₋₁₉)−30*X; or  Formula VIII (−8)*A1+(−1)*A2+(12)*A3+(7)*A4+(18)*A5+(12)*A6+(19)*A7+(6)*A8+(−4)*A9+(−5)*A10+(−2)*A11+(−5)*A12+(17)*A13+(−3)*A14+(4)*A15+(2)*A16+(8)*A17+(11)*A18+(30)*A19+(−13)*U1+(−10)*U2+(2)*U3+(−2)*U4+(−5)*U5+(5)*U6+(−2)*U7+(−10)*U8+(−5)*U9+(15)*U10+(−1)*U11+(0)*U12+(10)*U13+(−9)*U14+(−13)*U15+(−10)*U16+(3)*U17+(9)*U18+(9)*U19+(7)*C1+(3)*C2+(−21)*C3+(5)*C4+(−9)*C5+(−20)*C6+(−18)*C7+(−5)*C8+(5)*C9+(1)*C10+(2)*C11+(−5)*C12+(−3)*C13+(−6)*C14+(−2)*C15+(−5)*C16+(−3)*C17+(−12)*C18+(−18)*C19+(14)*G1+(8)*G2+(7)*G3+(−10)*G4+(−4)*G5+(2)*G6+(1)*G7+(9)*G8+(5)*G9+(−11)*G10+(1)*G11+(9)*G12+(−24)*G13+(18)*G14+(11)*G15+(13)*G16+(−7)*G17+(−9)*G18+(−22)*G19+6*(number of A+U in position 15-19)−3*(number of G+C in whole siRNA),  Formula X

wherein position numbering begins at the 5′-most position of a sense strand, and

A₁=1 if A is the base at position 1 of the sense strand, otherwise its value is 0;

A₂=1 if A is the base at position 2 of the sense strand, otherwise its value is 0;

A₃=1 if A is the base at position 3 of the sense strand, otherwise its value is 0;

A₄=1 if A is the base at position 4 of the sense strand, otherwise its value is 0;

A₅=1 if A is the base at position 5 of the sense strand, otherwise its value is 0;

A₆=1 if A is the base at position 6 of the sense strand, otherwise its value is 0;

A₇=1 if A is the base at position 7 of the sense strand, otherwise its value is 0;

A₁₀=1 if A is the base at position 10 of the sense strand, otherwise its value is 0;

A₁₁=1 if A is the base at position 11 of the sense strand, otherwise its value is 0;

A₁₃=1 if A is the base at position 13 of the sense strand, otherwise its value is 0;

A₁₉=1 if A is the base at position 19 of the sense strand, otherwise if another base is present or the sense strand is only 18 base pairs in length, its value is 0;

C₃=1 if C is the base at position 3 of the sense strand, otherwise its value is 0;

C₄=1 if C is the base at position 4 of the sense strand, otherwise its value is 0;

C₅=1 if C is the base at position 5 of the sense strand, otherwise its value is 0;

C₆=1 if C is the base at position 6 of the sense strand, otherwise its value is 0;

C₇=1 if C is the base at position 7 of the sense strand, otherwise its value is 0;

C₉=1 if C is the base at position 9 of the sense strand, otherwise its value is 0;

C₁₇=1 if C is the base at position 17 of the sense strand, otherwise its value is 0;

C₁₈=1 if C is the base at position 18 of the sense strand, otherwise its value is 0;

C₁₉=1 if C is the base at position 19 of the sense strand, otherwise if another base is present or the sense strand is only 18 base pairs in length, its value is 0;

G₁=1 if G is the base at position 1 on the sense strand, otherwise its value is 0;

G₂=1 if G is the base at position 2 of the sense strand, otherwise its value is 0;

G₈=1 if G is the base at position 8 on the sense strand, otherwise its value is 0;

G₁₀=1 if G is the base at position 10 on the sense strand, otherwise its value is 0;

-   -   G₁₃=1 if G is the base at position 13 on the sense strand,         otherwise its value is 0;         G₁₉=1 if G is the base at position 19 of the sense strand,         otherwise if another base is present or the sense strand is only         18 base pairs in length, its value is 0;         U₁=1 if U is the base at position 1 on the sense strand,         otherwise its value is 0;         U₂=1 if U is the base at position 2 on the sense strand,         otherwise its value is 0;         U₃=1 if U is the base at position 3 on the sense strand,         otherwise its value is 0;         U₄=1 if U is the base at position 4 on the sense strand,         otherwise its value is 0;         U₇=1 if U is the base at position 7 on the sense strand,         otherwise its value is 0;         U₉=1 if U is the base at position 9 on the sense strand,         otherwise its value is 0;         U₁₀=1 if U is the base at position 10 on the sense strand,         otherwise its value is 0;         U₁₅=1 if U is the base at position 15 on the sense strand,         otherwise its value is 0;         U₁₆=1 if U is the base at position 16 on the sense strand,         otherwise its value is 0;         U₁₇=1 if U is the base at position 17 on the sense strand,         otherwise its value is 0;         U₁₈=1 if U is the base at position 18 on the sense strand,         otherwise its value is 0.

GC₁₅₋₁₉=the number of G and C bases within positions 15-19 of the sense strand, or within positions 15-18 if the sense strand is only 18 base pairs in length;

GC_(total)=the number of G and C bases in the sense strand;

Tm=100 if the siRNA oligo has the internal repeat longer then 4 base pairs, otherwise its value is 0; and

X=the number of times that the same nucleotide repeats four or more times in a row.

Any of the methods of selecting siRNA in accordance with the invention can further comprise comparing the internal stability profiles of the siRNAs to be selected, and selecting those siRNAs with the most favorable internal stability profiles. Any of the methods of selecting siRNA can further comprise selecting either for or against sequences that contain motifs that induce cellular stress. Such motifs include, for example, toxicity motifs. Any of the methods of selecting siRNA can further comprise either selecting for or selecting against sequences that comprise stability motifs.

In another embodiment, the present invention provides a method of gene silencing, comprising introducing into a cell at least one siRNA selected according to any of the methods of the present invention. The siRNA can be introduced by allowing passive uptake of siRNA, or through the use of a vector.

According to a third embodiment, the invention provides a method for developing an algorithm for selecting siRNA, said method comprising: (a) selecting a set of siRNA; (b) measuring gene silencing ability of each siRNA from said set; (c) determining relative functionality of each siRNA; (d) determining improved functionality by the presence or absence of at least one variable selected from the group consisting of the presence or absence of a particular nucleotide at a particular position, the total number of As and Us in positions 15-19, the number of times that the same nucleotide repeats within a given sequence, and the total number of Gs and Cs; and (e) developing an algorithm using the information of step (d).

In another embodiment, the invention provides a method for selecting an siRNA with improved functionality, comprising using the above-mentioned algorithm to identify an siRNA of improved functionality.

According to a fourth embodiment, the present invention provides a kit, wherein said kit is comprised of at least two siRNAs, wherein said at least two siRNAs comprise a first optimized siRNA and a second optimized siRNA, wherein said first optimized siRNA and said second optimized siRNA are optimized according a formula comprising Formula X.

According to a fifth embodiment, the present invention provides a method for identifying a hyperfunctional siRNA, comprising applying selection criteria to a set of potential siRNA that comprise 18-30 base pairs, wherein said selection criteria are non-target specific criteria, and said set comprises at least two siRNAs and each of said at least two siRNAs contains a sequence that is at least substantially complementary to a target gene; determining the relative functionality of the at least two siRNAs and assigning each of the at least two siRNAs a functionality score; and selecting siRNAs from the at least two siRNAs that have a functionality score that reflects greater than 80 percent silencing at a concentration in the picomolar range, wherein said greater than 80 percent silencing endures for greater than 120 hours.

In other embodiments, the invention provides kits and/or methods wherein the siRNA are comprised of two separate polynucleotide strands; wherein the siRNA are comprised of a single contiguous molecule such as, for example, a unimolecular siRNA (comprising, for example, either a nucleotide or non-nucleotide loop); wherein the siRNA are expressed from one or more vectors; and wherein two or more genes are silenced by a single administration of siRNA.

According to a sixth embodiment, the present invention provides a hyperfunctional siRNA that is capable of silencing Bcl2.

According to a seventh embodiment, the present invention provides a method for developing an siRNA algorithm for selecting functional and hyperfunctional siRNAs for a given sequence. The method comprises:

(a) selecting a set of siRNAs;

(b) measuring the gene silencing ability of each siRNA from said set;

(c) determining the relative functionality of each siRNA;

(d) determining the amount of improved functionality by the presence or absence of at least one variable selected from the group consisting of the total GC content, melting temperature of the siRNA, GC content at positions 15-19, the presence or absence of a particular nucleotide at a particular position, relative thermodynamic stability at particular positions in a duplex, and the number of times that the same nucleotide repeats within a given sequence; and

(e) developing an algorithm using the information of step (d).

According to this embodiment, preferably the set of siRNAs comprises at least 90 siRNAs from at least one gene, more preferably at least 180 siRNAs from at least two different genes, and most preferably at least 270 and 360 siRNAs from at least three and four different genes, respectively. Additionally, in step (d) the determination is made with preferably at least two, more preferably at least three, even more preferably at least four, and most preferably all of the variables. The resulting algorithm is not target sequence specific.

In another embodiment, the present invention provides rationally designed siRNAs identified using the formulas above.

In yet another embodiment, the present invention is directed to hyperfunctional siRNA.

The ability to use the above algorithms, which are not sequence or species specific, allows for the cost-effective selection of optimized siRNAs for specific target sequences. Accordingly, there will be both greater efficiency and reliability in the use of siRNA technologies.

The methods disclosed herein can be used in conjunction with comparing internal stability profiles of selected siRNAs, and designing an siRNA with a desirable internal stability profile; and/or in conjunction with a selection either for or against sequences that contain motifs that induce cellular stress, for example, cellular toxicity.

Any of the methods disclosed herein can be used to silence one or more genes by introducing an siRNA selected, or designed, in accordance with any of the methods disclosed herein. The siRNA(s) can be introduced into the cell by any method known in the art, including passive uptake or through the use of one or more vectors.

Any of the methods and kits disclosed herein can employ either unimolecular siRNAs, siRNAs comprised of two separate polynucleotide strands, or combinations thereof. Any of the methods disclosed herein can be used in gene silencing, where two or more genes are silenced by a single administration of siRNA(s). The siRNA(s) can be directed against two or more target genes, and administered in a single dose or single transfection, as the case may be.

Optimizing siRNA

According to one embodiment, the present invention provides a method for improving the effectiveness of gene silencing for use to silence a particular gene through the selection of an optimal siRNA. An siRNA selected according to this method may be used individually, or in conjunction with the first embodiment, i.e., with one or more other siRNAs, each of which may or may not be selected by this criteria in order to maximize their efficiency.

The degree to which it is possible to select an siRNA for a given mRNA that maximizes these criteria will depend on the sequence of the mRNA itself. However, the selection criteria will be independent of the target sequence. According to this method, an siRNA is selected for a given gene by using a rational design. That said, rational design can be described in a variety of ways. Rational design is, in simplest terms, the application of a proven set of criteria that enhance the probability of identifying a functional or hyperfunctional siRNA. In one method, rationally designed siRNA can be identified by maximizing one or more of the following criteria:

(1) A low GC content, preferably between about 30-52%.

(2) At least 2, preferably at least 3 A or U bases at positions 15-19 of the siRNA on the sense strand.

(3) An A base at position 19 of the sense strand.

(4) An A base at position 3 of the sense strand.

(5) A U base at position 10 of the sense strand.

(6) An A base at position 14 of the sense strand.

(7) A base other than C at position 19 of the sense strand.

(8) A base other than G at position 13 of the sense strand.

(9) A Tm, which refers to the character of the internal repeat that results in inter- or intramolecular structures for one strand of the duplex, that is preferably not stable at greater than 50° C., more preferably not stable at greater than 37° C., even more preferably not stable at greater than 30° C. and most preferably not stable at greater than 20° C.

(10) A base other than U at position 5 of the sense strand.

(11) A base other than A at position 11 of the sense strand.

(12) A base other than an A at position 1 of the sense strand.

(13) A base other than an A at position 2 of the sense strand.

(14) An A base at position 4 of the sense strand.

(15) An A base at position 5 of the sense strand.

(16) An A base at position 6 of the sense strand.

(17) An A base at position 7 of the sense strand.

(18) An A base at position 8 of the sense strand.

(19) A base other than an A at position 9 of the sense strand.

(20) A base other than an A at position 10 of the sense strand.

(21) A base other than an A at position 11 of the sense strand.

(22) A base other than an A at position 12 of the sense strand.

(23) An A base at position 13 of the sense strand.

(24) A base other than an A at position 14 of the sense strand.

(25) An A base at position 15 of the sense strand

(26) An A base at position 16 of the sense strand.

(27) An A base at position 17 of the sense strand.

(28) An A base at position 18 of the sense strand.

(29) A base other than a U at position 1 of the sense strand.

(30) A base other than a U at position 2 of the sense strand.

(31) A U base at position 3 of the sense strand.

(32) A base other than a U at position 4 of the sense strand.

(33) A base other than a U at position 5 of the sense strand.

(34) A U base at position 6 of the sense strand.

(35) A base other than a U at position 7 of the sense strand.

(36) A base other than a U at position 8 of the sense strand.

(37) A base other than a U at position 9 of the sense strand.

(38) A base other than a U at position 11 of the sense strand.

(39) A U base at position 13 of the sense strand.

(40) A base other than a U at position 14 of the sense strand.

(41) A base other than a U at position 15 of the sense strand.

(42) A base other than a U at position 16 of the sense strand.

(43) A U base at position 17 of the sense strand.

(44) A U base at position 18 of the sense strand.

(45) A U base at position 19 of the sense strand.

(46) A C base at position 1 of the sense strand.

(47) A C base at position 2 of the sense strand.

(48) A base other than a C at position 3 of the sense strand.

(49) A C base at position 4 of the sense strand.

(50) A base other than a C at position 5 of the sense strand.

(51) A base other than a C at position 6 of the sense strand.

(52) A base other than a C at position 7 of the sense strand.

(53) A base other than a C at position 8 of the sense strand.

(54) A C base at position 9 of the sense strand.

(55) A C base at position 10 of the sense strand.

(56) A C base at position 11 of the sense strand.

(57) A base other than a C at position 12 of the sense strand.

(58) A base other than a C at position 13 of the sense strand.

(59) A base other than a C at position 14 of the sense strand.

(60) A base other than a C at position 15 of the sense strand.

(61) A base other than a C at position 16 of the sense strand.

(62) A base other than a C at position 17 of the sense strand.

(63) A base other than a C at position 18 of the sense strand.

(64) A G base at position 1 of the sense strand.

(65) A G base at position 2 of the sense strand.

(66) A G base at position 3 of the sense strand.

(67) A base other than a G at position 4 of the sense strand.

(68) A base other than a G at position 5 of the sense strand.

(69) A G base at position 6 of the sense strand.

(70) A G base at position 7 of the sense strand.

(71) A G base at position 8 of the sense strand.

(72) A G base at position 9 of the sense strand.

(73) A base other than a G at position 10 of the sense strand.

(74) A G base at position 11 of the sense strand.

(75) A G base at position 12 of the sense strand.

(76) A G base at position 14 of the sense strand.

(77) A G base at position 15 of the sense strand.

(78) A G base at position 16 of the sense strand.

(79) A base other than a G at position 17 of the sense strand.

(80) A base other than a G at position 18 of the sense strand.

(81) A base other than a G at position 19 of the sense strand.

The importance of various criteria can vary greatly. For instance, a C base at position 10 of the sense strand makes a minor contribution to duplex functionality. In contrast, the absence of a C at position 3 of the sense strand is very important. Accordingly, preferably an siRNA will satisfy as many of the aforementioned criteria as possible.

With respect to the criteria, GC content, as well as a high number of AU in positions 15-19 of the sense strand, may be important for easement of the unwinding of double stranded siRNA duplex. Duplex unwinding has been shown to be crucial for siRNA functionality in vivo.

With respect to criterion 9, the internal structure is measured in terms of the melting temperature of the single strand of siRNA, which is the temperature at which 50% of the molecules will become denatured. With respect to criteria 2-8 and 10-11, the positions refer to sequence positions on the sense strand, which is the strand that is identical to the mRNA.

In one preferred embodiment, at least criteria 1 and 8 are satisfied. In another preferred embodiment, at least criteria 7 and 8 are satisfied. In still another preferred embodiment, at least criteria 1, 8 and 9 are satisfied.

It should be noted that all of the aforementioned criteria regarding sequence position specifics are with respect to the 5′ end of the sense strand. Reference is made to the sense strand, because most databases contain information that describes the information of the mRNA. Because according to the present invention a chain can be from 18 to 30 bases in length, and the aforementioned criteria assumes a chain 19 base pairs in length, it is important to keep the aforementioned criteria applicable to the correct bases.

When there are only 18 bases, the base pair that is not present is the base pair that is located at the 3′ of the sense strand. When there are twenty to thirty bases present, then additional bases are added at the 5′ end of the sense chain and occupy positions −1 to −11. Accordingly, with respect to SEQ. ID NO. 0001 NNANANNNNUCNAANNNNA and SEQ. ID NO. 0028 GUCNNANANNNNUCNAANNNNA, both would have A at position 3, A at position 5, U at position 10, C at position 11, A and position 13, A and position 14 and A at position 19. However, SEQ. ID NO. 0028 would also have C at position −1, U at position −2 and G at position −3.

For a 19 base pair siRNA, an optimal sequence of one of the strands may be represented below, where N is any base, A, C, G, or U: SEQ. ID NO. 0001. NNANANNNNUCNAANNNNA SEQ. ID NO. 0002. NNANANNNNUGNAANNNNA SEQ. ID NO. 0003. NNANANNNNUUNAANNNNA SEQ. ID NO. 0004. NNANANNNNUCNCANNNNA SEQ. ID NO. 0005. NNANANNNNUGNCANNNNA SEQ. ID NO. 0006. NNANANNNNUUNCANNNNA SEQ. ID NO. 0007. NNANANNNNUCNUANNNNA SEQ. ID NO. 0008. NNANANNNNUGNUANNNNA SEQ. ID NO. 0009. NNANANNNNUUNUANNNNA SEQ. ID NO. 0010. NNANCNNNNUCNAANNNNA SEQ. ID NO. 0011. NNANCNNNNUGNAANNNNA SEQ. ID NO. 0012. NNANCNNNNUUNAANNNNA SEQ. ID NO. 0013. NNANCNNNNUCNCANNNNA SEQ. ID NO. 0014. NNANCNNNNUGNCANNNNA SEQ. ID NO. 0015. NNANCNNNNUUNCANNNNA SEQ. ID NO. 0016. NNANCNNNNUCNUANNNNA SEQ. ID NO. 0017. NNANCNNNNUGNUANNNNA SEQ. ID NO. 0018. NNANCNNNNUUNUANNNNA SEQ. ID NO. 0019. NNANGNNNNUCNAANNNNA SEQ. ID NO. 0020. NNANGNNNNUGNAANNNNA SEQ. ID NO. 0021. NNANGNNNNUUNAANNNNA SEQ. ID NO. 0022. NNANGNNNNUCNCANNNNA SEQ. ID NO. 0023. NNANGNNNNUGNCANNNNA SEQ. ID NO. 0024. NNANGNNNNUUNCANNNNA SEQ. ID NO. 0025. NNANGNNNNUCNUANNNNA SEQ. ID NO. 0026. NNANGNNNNUGNUANNNNA SEQ. ID NO. 0027. NNANGNNNNNUNUANNNNA

In one embodiment, the sequence used as an siRNA is selected by choosing the siRNA that score highest according to one of the following seven algorithms that are represented by Formulas I-VII: Relative functionality of siRNA=−(GC/3)+(AU ₁₅₋₁₉)−(Tm _(20° C.))*3−(G ₁₃)*3−(C ₁₉)+(A ₁₉)*2+(A ₃)+(U ₁₀)+(A ₁₄)−(U ₅)−(A ₁₁)  Formula I Relative functionality of siRNA=−(GC/3)−(AU ₁₅₋₁₉)*3−(G ₁₃)*3−(C ₁₉)+(A ₁₉)*2+(A ₃)  Formula II Relative functionality of siRNA=−(GC/3)+(AU ₁₅₋₁₉)−(Tm _(20° C.))*3  Formula III Relative functionality of siRNA=−GC/2+(AU ₁₅₋₁₉)/2−(Tm _(20° C.)*)2−(G ₁₃)*3−(C ₁₉)+(A ₁₉)*2+(A ₃)+(U ₁₀)+(A ₁₄)−(U ₅)−(A ₁₁)  Formula IV Relative functionality of siRNA=−(G ₁₃)*3−(C ₁₉)+(A ₁₉)*2+(A ₃)+(U ₁₀)+(A ₁₄)−(U ₅)−(A ₁₁)  Formula V Relative functionality of siRNA=−(G ₁₃)*3−(C ₁₉)+(A ₁₉)*2+(A ₃)  Formula VI Relative functionality of siRNA=−(GC/2)+(AU ₁₅₋₁₉)/2−(Tm _(20° C.))*1−(G ₁₃)*3−(C ₁₉)+(A ₁₉)*3+(A ₃)*3+(U ₁₀)/2+(A ₁₄)/2−(U ₅)/2−(A ₁₁)/2  Formula VII

In Formulas I-VII:

wherein A₁₉=1 if A is the base at position 19 on the sense strand, otherwise its value is 0,

AU₁₅₋₁₉=0-5 depending on the number of A or U bases on the sense strand at positions 15-19;

G₁₃=1 if G is the base at position 13 on the sense strand, otherwise its value is 0;

C₁₉=1 if C is the base at position 19 of the sense strand, otherwise its value is 0;

GC=the number of G and C bases in the entire sense strand;

Tm_(20° C.)=1 if the Tm is greater than 20° C.;

A₃=1 if A is the base at position 3 on the sense strand, otherwise its value is 0;

U₁₀=1 if U is the base at position 10 on the sense strand, otherwise its value is 0;

A₁₄=1 if A is the base at position 14 on the sense strand, otherwise its value is 0;

U₅=1 if U is the base at position 5 on the sense strand, otherwise its value is 0; and

A₁₁=1 if A is the base at position 11 of the sense strand, otherwise its value is 0.

Formulas I-VII provide relative information regarding functionality. When the values for two sequences are compared for a given formula, the relative functionality is ascertained; a higher positive number indicates a greater functionality. For example, in many applications a value of 5 or greater is beneficial.

Additionally, in many applications, more than one of these formulas would provide useful information as to the relative functionality of potential siRNA sequences. However, it is beneficial to have more than one type of formula, because not every formula will be able to help to differentiate among potential siRNA sequences. For example, in particularly high GC mRNAs, formulas that take that parameter into account would not be useful and application of formulas that lack GC elements (e.g., formulas V and VI) might provide greater insights into duplex functionality. Similarly, formula II might by used in situations where hairpin structures are not observed in duplexes, and formula IV might be applicable for sequences that have higher AU content. Thus, one may consider a particular sequence in light of more than one or even all of these algorithms to obtain the best differentiation among sequences. In some instances, application of a given algorithm may identify an unusually large number of potential siRNA sequences, and in those cases, it may be appropriate to re-analyze that sequence with a second algorithm that is, for instance, more stringent. Alternatively, it is conceivable that analysis of a sequence with a given formula yields no acceptable siRNA sequences (i.e. low SMARTSCORES™, or siRNA ranking). In this instance, it may be appropriate to re-analyze that sequences with a second algorithm that is, for instance, less stringent. In still other instances, analysis of a single sequence with two separate formulas may give rise to conflicting results (i.e. one formula generates a set of siRNA with high SMARTSCORES™, or siRNA ranking, while the other formula identifies a set of siRNA with low SMARTSCORES™, or siRNA ranking). In these instances, it may be necessary to determine which weighted factor(s) (e.g. GC content) are contributing to the discrepancy and assessing the sequence to decide whether these factors should or should not be included. Alternatively, the sequence could be analyzed by a third, fourth, or fifth algorithm to identify a set of rationally designed siRNA.

The above-referenced criteria are particularly advantageous when used in combination with pooling techniques as depicted in Table I: TABLE I FUNCTIONAL PROBABILITY OLIGOS POOLS CRITERIA >95% >80% <70% >95% >80% <70% CURRENT 33.0 50.0 23.0 79.5 97.3 0.3 NEW 50.0 88.5 8.0 93.8 99.98 0.005 (GC) 28.0 58.9 36.0 72.8 97.1 1.6

The term “current” used in Table I refers to Tuschl's conventional siRNA parameters (Elbashir, S. M. et al. (2002) “Analysis of gene function in somatic mammalian cells using small interfering RNAs” Methods 26: 199-213). “New” refers to the design parameters described in Formulas I-VII. “GC” refers to criteria that select siRNA solely on the basis of GC content.

As Table I indicates, when more functional siRNA duplexes are chosen, siRNAs that produce <70% silencing drops from 23% to 8% and the number of siRNA duplexes that produce >80% silencing rises from 50% to 88.5%. Further, of the siRNA duplexes with >80% silencing, a larger portion of these siRNAs actually silence >95% of the target expression (the new criteria increases the portion from 33% to 50%). Using this new criteria in pooled siRNAs, shows that, with pooling, the amount of silencing >95% increases from 79.5% to 93.8% and essentially eliminates any siRNA pool from silencing less than 70%.

Table II similarly shows the particularly beneficial results of pooling in combination with the aforementioned criteria. However, Table II, which takes into account each of the aforementioned variables, demonstrates even a greater degree of improvement in functionality. TABLE II FUNCTIONAL PROBABILITY OLIGOS POOLS NON- NON- FUNCTIONAL AVERAGE FUNCTIONAL FUNCTIONAL AVERAGE FUNCTIONAL RANDOM 20 40 50 67 97 3 CRITERIA 1 52 99 0.1 97 93 0.0040 CRITERIA 4 89 99 0.1 99 99 0.0000

The terms “functional,” “Average,” and “Non-functional” used in Table II, refer to siRNA that exhibit >80%, >50%, and <50% functionality, respectively. Criteria 1 and 4 refer to specific criteria described above.

The above-described algorithms may be used with or without a computer program that allows for the inputting of the sequence of the mRNA and automatically outputs the optimal siRNA. The computer program may, for example, be accessible from a local terminal or personal computer, over an internal network or over the Internet.

In addition to the formulas above, more detailed algorithms may be used for selecting siRNA. Preferably, at least one RNA duplex of 18-30 base pairs is selected such that it is optimized according a formula selected from: (−14)*G₁₃−13*A₁−12*U₇−11*U₂−10*A₁₁−10*U₄−10*C₃−10*C₅−10*C₆−9*A₁₀−9*U₉−9*C₁₈−8*G₁₀−7*U₁−7*U₁₆−7*C₁₇−7*C₁₉+7*U₁₇+8*A₂+8*A₄+8*A₅+8*C₄+9*G₈+10*A₇+10*U₁₈+11*A₁₉+11*C₉+15*G₁+18*A₃+19*U₁₀−Tm−3*(GC_(total)−)6*(GC₁₅₋₁₉)−30*X; and  Formula VIII (14.1)*A₃+(14.9)*A₆+(17.6)*A₁₃+(24.7)*A₁₉+(14.2)*U₁₀+(10.5)*C₉+(23.9)*G₁+(16.3)*G₂+(−12.3)*A₁₁+(−19.3)*U₁+(−12.1)*U₂+(−11)*U₃+(−15.2)*U₁₅+(−11.3)*U₁₆+(−11.8)*C₃+(−17.4)*C₆+(−10.5)*C₇+(−13.7)*G₁₃+(−25.9)*G₁₉−Tm−3*(GC_(total))−6*(GC₁₅₋₁₉)−30*X; and  Formula IX (−8)*A1+(−1)*A2+(12)*A3+(7)*A4+(18)*A5+(12)*A6+(19)*A7+(6)*A8+(−4)*A9+(−5)*A10+(−2)*A11+(−5)*A12+(17)*A13+(−3)*A14+(4)*A15+(2)*A16+(8)*A17+(11)*A18+(30)*A19+(−13)*U1+(−10)*U2+(2)*U3+(−2)*U4+(−5)*U5+(5)*U6+(−2)*U7+(−10)*U8+(−5)*U9+(15)*U10+(−1)*U11+(0)*U12+(10)*U13+(−9)*U14+(−13)*U15+(−10)*U16+(3)*U17+(9)*U18+(9)*U19+(7)*C1+(3)*C2+(−21)*C3+(5)*C4+(−9)*C5+(−20)*C6+(−18)*C7+(−5)*C8+(5)*C9+(1)*C10+(2)*C11+(−5)*C12+(−3)*C13+(−6)*C14+(−2)*C15+(−5)*C16+(−3)*C17+(−12)*C18+(−18)*C19+(14)*G1+(8)*G2+(7)*G3+(−10)*G4+(−4)*G5+(2)*G6+(1)*G7+(9)*G8+(5)*G9+(−11)*G10+(1)*G11+(9)*G12+(−24)*G13+(18)*G14+(11)*G15+(13)*G16+(−7)*G17+(−9)*G18+(−22)*G19+6*(number of A+U in position 15-19)−3*(number of G+C in whole siRNA).  Formula X

wherein

A₁=1 if A is the base at position 1 of the sense strand, otherwise its value is 0;

A₂=1 if A is the base at position 2 of the sense strand, otherwise its value is 0;

A₃=1 if A is the base at position 3 of the sense strand, otherwise its value is 0;

A₄=1 if A is the base at position 4 of the sense strand, otherwise its value is 0;

A₅=1 if A is the base at position 5 of the sense strand, otherwise its value is 0;

A₆=1 if A is the base at position 6 of the sense strand, otherwise its value is 0;

A₇=1 if A is the base at position 7 of the sense strand, otherwise its value is 0;

A₁₀=1 if A is the base at position 10 of the sense strand, otherwise its value is 0;

A₁₁=1 if A is the base at position 11 of the sense strand, otherwise its value is 0;

A₁₃=1 if A is the base at position 13 of the sense strand, otherwise its value is 0;

A₁₉=1 if A is the base at position 19 of the sense strand, otherwise if another base is present or the sense strand is only 18 base pairs in length, its value is 0;

C₃=1 if C is the base at position 3 of the sense strand, otherwise its value is 0;

C₄=1 if C is the base at position 4 of the sense strand, otherwise its value is 0;

C₅=1 if C is the base at position 5 of the sense strand, otherwise its value is 0;

C₆=1 if C is the base at position 6 of the sense strand, otherwise its value is 0;

C₇=1 if C is the base at position 7 of the sense strand, otherwise its value is 0;

C₉=1 if C is the base at position 9 of the sense strand, otherwise its value is 0;

C₁₇=1 if C is the base at position 17 of the sense strand, otherwise its value is 0;

C₁₈=1 if C is the base at position 18 of the sense strand, otherwise its value is 0;

C₁₉=1 if C is the base at position 19 of the sense strand, otherwise if another base is present or the sense strand is only 18 base pairs in length, its value is 0;

G₁=1 if G is the base at position 1 on the sense strand, otherwise its value is 0;

G₂=1 if G is the base at position 2 of the sense strand, otherwise its value is 0;

G₈=1 if G is the base at position 8 on the sense strand, otherwise its value is 0;

G₁₀=1 if G is the base at position 10 on the sense strand, otherwise its value is 0;

G₁₃=1 if G is the base at position 13 on the sense strand, otherwise its value is 0;

G₁₉=1 if G is the base at position 19 of the sense strand, otherwise if another base is present or the sense strand is only 18 base pairs in length, its value is 0;

U₁=1 if U is the base at position 1 on the sense strand, otherwise its value is 0;

U₂=1 if U is the base at position 2 on the sense strand, otherwise its value is 0;

U₃=1 if U is the base at position 3 on the sense strand, otherwise its value is 0;

U₄=1 if U is the base at position 4 on the sense strand, otherwise its value is 0;

U₇=1 if U is the base at position 7 on the sense strand, otherwise its value is 0;

U₉=1 if U is the base at position 9 on the sense strand, otherwise its value is 0;

U₁₀=1 if U is the base at position 10 on the sense strand, otherwise its value is 0;

U₁₅=1 if U is the base at position 15 on the sense strand, otherwise its value is 0;

U₁₆=1 if U is the base at position 16 on the sense strand, otherwise its value is 0;

U₁₇=1 if U is the base at position 17 on the sense strand, otherwise its value is 0;

U₁₈=1 if U is the base at position 18 on the sense strand, otherwise its value is 0;

GC₁₅₋₁₉=the number of G and C bases within positions 15-19 of the sense strand, or within positions 15-18 if the sense strand is only 18 base pairs in length;

GC_(total)=the number of G and C bases in the sense strand;

Tm=100 if the siRNA oligo has the internal repeat longer then 4 base pairs, otherwise its value is 0; and

X=the number of times that the same nucleotide repeats four or more times in a row.

The above formulas VIII, IX, and X, as well as formulas I-VII, provide methods for selecting siRNA in order to increase the efficiency of gene silencing. A subset of variables of any of the formulas may be used, though when fewer variables are used, the optimization hierarchy becomes less reliable.

With respect to the variables of the above-referenced formulas, a single letter of A or C or G or U followed by a subscript refers to a binary condition. The binary condition is that either the particular base is present at that particular position (wherein the value is “1”) or the base is not present (wherein the value is “0”). Because position 19 is optional, i.e., there might be only 18 base pairs, when there are only 18 base pairs, any base with a subscript of 19 in the formulas above would have a zero value for that parameter. Before or after each variable is a number followed by *, which indicates that the value of the variable is to be multiplied or weighed by that number.

The numbers preceding the variables A, or G, or C, or U in Formulas VIII, IX, and X (or after the variables in Formula I-VII) were determined by comparing the difference in the frequency of individual bases at different positions in functional siRNA and total siRNA. Specifically, the frequency in which a given base was observed at a particular position in functional groups was compared with the frequency that that same base was observed in the total, randomly selected siRNA set. If the absolute value of the difference between the functional and total values was found to be greater than 6%, that parameter was included in the equation. Thus, for instance, if the frequency of finding a “G” at position 13 (G₁₃) is found to be 6% in a given functional group, and the frequency of G₁₃ in the total population of siRNAs is 20%, the difference between the two values is 6%-20%=−14%. As the absolute value is greater than six (6), this factor (−14) is included in the equation. Thus, in Formula VIII, in cases where the siRNA under study has a G in position 13, the accrued value is (−14)*(1)=−14. In contrast, when a base other than G is found at position 13, the accrued value is (−14)*(0)=0.

When developing a means to optimize siRNAs, the inventors observed that a bias toward low internal thermodynamic stability of the duplex at the 5′-antisense (AS) end is characteristic of naturally occurring miRNA precursors. The inventors extended this observation to siRNAs for which functionality had been assessed in tissue culture.

With respect to the parameter GC₁₅₋₁₉, a value of 0-5 will be ascribed depending on the number of G or C bases at positions 15 to 19. If there are only 18 base pairs, the value is between 0 and 4.

With respect to the criterion GC_(total) content, a number from 0-30 will be ascribed, which correlates to the total number of G and C nucleotides on the sense strand, excluding overhangs. Without wishing to be bound by any one theory, it is postulated that the significance of the GC content (as well as AU content at positions 15-19, which is a parameter for formulas III-VII) relates to the easement of the unwinding of a double-stranded siRNA duplex. Duplex unwinding is believed to be crucial for siRNA functionality in vivo and overall low internal stability, especially low internal stability of the first unwound base pair is believed to be important to maintain sufficient processivity of RISC complex-induced duplex unwinding. If the duplex has 19 base pairs, those at positions 15-19 on the sense strand will unwind first if the molecule exhibits a sufficiently low internal stability at that position. As persons skilled in the art are aware, RISC is a complex of approximately twelve proteins; Dicer is one, but not the only, helicase within this complex. Accordingly, although the GC parameters are believed to relate to activity with Dicer, they are also important for activity with other RISC proteins.

The value of the parameter Tm is 0 when there are no internal repeats longer than (or equal to) four base pairs present in the siRNA duplex; otherwise the value is 1. Thus for example, if the sequence ACGUACGU, or any other four nucleotide (or more) palindrome exists within the structure, the value will be one (1). Alternatively if the structure ACGGACG, or any other 3 nucleotide (or less) palindrome exists, the value will be zero (0).

The variable “X” refers to the number of times that the same nucleotide occurs contiguously in a stretch of four or more units. If there are, for example, four contiguous As in one part of the sequence and elsewhere in the sequence four contiguous Cs, X=2. Further, if there are two separate contiguous stretches of four of the same nucleotides or eight or more of the same nucleotides in a row, then X=2. However, X does not increase for five, six or seven contiguous nucleotides.

Again, when applying Formula VIII, Formula IX, or Formula X, to a given mRNA, (the “target RNA” or “target molecule”), one may use a computer program to evaluate the criteria for every sequence of 18-30 base pairs or only sequences of a fixed length, e.g., 19 base pairs. Preferably the computer program is designed such that it provides a report ranking of all of the potential siRNAs 18-30 base pairs, ranked according to which sequences generate the highest value. A higher value refers to a more efficient siRNA for a particular target gene. The computer program that may be used may be developed in any computer language that is known to be useful for scoring nucleotide sequences, or it may be developed with the assistance of commercially available product such as Microsoft's PRODUCT.NET. Additionally, rather than run every sequence through one and/or another formula, one may compare a subset of the sequences, which may be desirable if for example only a subset are available. For instance, it may be desirable to first perform a BLAST (Basic Local Alignment Search Tool) search and to identify sequences that have no homology to other targets. Alternatively, it may be desirable to scan the sequence and to identify regions of moderate GC context, then perform relevant calculations using one of the above-described formulas on these regions. These calculations can be done manually or with the aid of a computer.

As with Formulas I-VII, either Formula VIII, Formula IX, or Formula X may be used for a given mRNA target sequence. However, it is possible that according to one or the other formula more than one siRNA will have the same value. Accordingly, it is beneficial to have a second formula by which to differentiate sequences. Formulas IX and X were derived in a similar fashion as Formula VIII, yet used a larger data set and thus yields sequences with higher statistical correlations to highly functional duplexes. The sequence that has the highest value ascribed to it may be referred to as a “first optimized duplex.” The sequence that has the second highest value ascribed to it may be referred to as a “second optimized duplex.” Similarly, the sequences that have the third and fourth highest values ascribed to them may be referred to as a third optimized duplex and a fourth optimized duplex, respectively. When more than one sequence has the same value, each of them may, for example, be referred to as first optimized duplex sequences or co-first optimized duplexes. Formula X is similar to Formula IX, yet uses a greater numbers of variables and for that reason, identifies sequences on the basis of slightly different criteria.

It should also be noted that the output of a particular algorithm will depend on several of variables including: (1) the size of the data base(s) being analyzed by the algorithm, and (2) the number and stringency of the parameters being applied to screen each sequence. Thus, for example, in U.S. patent application Ser. No. 10/714,333, entitled “Functional and Hyperfunctional siRNA,” filed Nov. 14, 2003, Formula VIII was applied to the known human genome (NCBI REFSEQ database) through ENTREZ (EFETCH). As a result of these procedures, roughly 1.6 million siRNA sequences were identified. Application of Formula VIII to the same database in March of 2004 yielded roughly 2.2 million sequences, a difference of approximately 600,000 sequences resulting from the growth of the database over the course of the months that span this period of time. Application of other formulas (e.g., Formula X) that change the emphasis of, include, or eliminate different variables can yield unequal numbers of siRNAs. Alternatively, in cases where application of one formula to one or more genes fails to yield sufficient numbers of siRNAs with scores that would be indicative of strong silencing, said genes can be reassessed with a second algorithm that is, for instance, less stringent.

siRNA sequences identified using Formula VIII and Formula X (minus sequences generated by Formula VIII) are contained within the sequence listing. The data included in the sequence listing is described more fully below. The sequences identified by Formula VIII and Formula X that are disclosed in the sequence listing may be used in gene silencing applications.

It should be noted that for Formulas VIII, IX, and X all of the aforementioned criteria are identified as positions on the sense strand when oriented in the 5′ to 3′ direction as they are identified in connection with Formulas I-VII unless otherwise specified.

Formulas I-X, may be used to select or to evaluate one, or more than one, siRNA in order to optimize silencing. Preferably, at least two optimized siRNAs that have been selected according to at least one of these formulas are used to silence a gene, more preferably at least three and most preferably at least four. The siRNAs may be used individually or together in a pool or kit. Further, they may be applied to a cell simultaneously or separately. Preferably, the at least two siRNAs are applied simultaneously. Pools are particularly beneficial for many research applications. However, for therapeutics, it may be more desirable to employ a single hyperfunctional siRNA as described elsewhere in this application.

When planning to conduct gene silencing, and it is necessary to choose between two or more siRNAs, one should do so by comparing the relative values when the siRNA are subjected to one of the formulas above. In general a higher scored siRNA should be used.

Useful applications include, but are not limited to, target validation, gene functional analysis, research and drug discovery, gene therapy and therapeutics. Methods for using siRNA in these applications are well known to persons of skill in the art.

Because the ability of siRNA to function is dependent on the sequence of the RNA and not the species into which it is introduced, the present invention is applicable across a broad range of species, including but not limited to all mammalian species, such as humans, dogs, horses, cats, cows, mice, hamsters, chimpanzees and gorillas, as well as other species and organisms such as bacteria, viruses, insects, plants and C. elegans.

The present invention is also applicable for use for silencing a broad range of genes, including but not limited to the roughly 45,000 genes of a human genome, and has particular relevance in cases where those genes are associated with diseases such as diabetes, Alzheimer's, cancer, as well as all genes in the genomes of the aforementioned organisms.

The siRNA selected according to the aforementioned criteria or one of the aforementioned algorithms are also, for example, useful in the simultaneous screening and functional analysis of multiple genes and gene families using high throughput strategies, as well as in direct gene suppression or silencing.

Development of the Algorithms

To identify siRNA sequence features that promote functionality and to quantify the importance of certain currently accepted conventional factors—such as G/C content and target site accessibility—the inventors synthesized an siRNA panel consisting of 270 siRNAs targeting three genes, Human Cyclophilin, Firefly Luciferase, and Human DBI. In all three cases, siRNAs were directed against specific regions of each gene. For Human Cyclophilin and Firefly Luciferase, ninety siRNAs were directed against a 199 bp segment of each respective mRNA. For DBI, 90 siRNAs were directed against a smaller, 109 base pair region of the mRNA. The sequences to which the siRNAs were directed are provided below.

It should be noted that in certain sequences, “t” is present. This is because many databases contain information in this manner. However, the t denotes a uracil residue in mRNA and siRNA. Any algorithm will, unless otherwise specified, process at in a sequence as a u.

Human Cyclophilin: 193-390, M60857 SEQ. ID NO. 29: gttccaaaaa cagtggataa ttttgtggcc ttagctacag gagagaaagg atttggctac aaaaacagca aattccatcg tgtaatcaag gacttcatga tccagggcgg agacttcacc aggggagatg gcacaggagg aaagagcatc tacggtgagc gcttccccga tgagaacttc aaactgaagc actacgggcc tggctggg

Firefly Luciferase: 1434-1631, U47298 (pGL3, Promega) SEQ. ID NO. 30: tgaacttccc gccgccgttq ttgttttgga gcacggaaag acgatgacgg aaaaagagat cgtggattac gtcgccagtc aagtaacaac cgcgaaaaag ttgcgcggag gagttgtgtt tgtggacgaa gtaccgaaag gtcttaccgg aaaactcgac gcaagaaaaa toagagagat cctcataaag gccaagaagg

DBI, NM_(—)020548 (202-310) (Every Position) SEQ. ID NO. 0031: acgggcaagg ccaagtggga tgcctggaat gagctgaaag ggacttccaa ggaagatgcc atgaaagctt acatcaacaa agtagaagag ctaaagaaaa aatacggg

A list of the siRNAs appears in Table III (see Examples Section, Example II)

The set of duplexes was analyzed to identify correlations between siRNA functionality and other biophysical or thermodynamic properties. When the siRNA panel was analyzed in functional and non-functional subgroups, certain nucleotides were much more abundant at certain positions in functional or non-functional groups. More specifically, the frequency of each nucleotide at each position in highly functional siRNA duplexes was compared with that of nonfunctional duplexes in order to assess the preference for or against any given nucleotide at every position. These analyses were used to determine important criteria to be included in the siRNA algorithms (Formulas VIII, IX, and X).

The data set was also analyzed for distinguishing biophysical properties of siRNAs in the functional group, such as optimal percent of GC content, propensity for internal structures and regional thermodynamic stability. Of the presented criteria, several are involved in duplex recognition, RISC activation/duplex unwinding, and target cleavage catalysis.

The original data set that was the source of the statistically derived criteria is shown in FIG. 2. Additionally, this figure shows that random selection yields siRNA duplexes with unpredictable and widely varying silencing potencies as measured in tissue culture using HEK293 cells. In the figure, duplexes are plotted such that each x-axis tick-mark represents an individual siRNA, with each subsequent siRNA differing in target position by two nucleotides for Human Cyclophilin B and Firefly Luciferase, and by one nucleotide for Human DBI. Furthermore, the y-axis denotes the level of target expression remaining after transfection of the duplex into cells and subsequent silencing of the target.

siRNA identified and optimized in this document work equally well in a wide range of cell types. FIG. 3 a shows the evaluation of thirty siRNAs targeting the DBI gene in three cell lines derived from different tissues. Each DBI siRNA displays very similar functionality in HEK293 (ATCC, CRL-1573, human embryonic kidney), HeLa (ATCC, CCL-2, cervical epithelial adenocarcinoma) and DU145 (HTB-81, prostate) cells as determined by the B-DNA assay. Thus, siRNA functionality is determined by the primary sequence of the siRNA and not by the intracellular environment. Additionally, it should be noted that although the present invention provides for a determination of the functionality of siRNA for a given target, the same siRNA may silence more than one gene. For example, the complementary sequence of the silencing siRNA may be present in more than one gene. Accordingly, in these circumstances, it may be desirable not to use the siRNA with highest SMARTSCORE™, or siRNA ranking. In such circumstances, it may be desirable to use the siRNA with the next highest SMARTSCORE™, or siRNA ranking.

To determine the relevance of G/C content in siRNA function, the G/C content of each duplex in the panel was calculated and the functional classes of siRNAs (<F50, ≧F50, ≧F80, ≧F95 where F refers to the percent gene silencing) were sorted accordingly. The majority of the highly-functional siRNAs (≧F95) fell within the G/C content range of 36%-52% (FIG. 3B). Twice as many non-functional (<F50) duplexes fell within the high G/C content groups (>57% GC content) compared to the 36%-52% group. The group with extremely low GC content (26% or less) contained a higher proportion of non-functional siRNAs and no highly-functional siRNAs. The G/C content range of 30%-52% was therefore selected as Criterion I for siRNA functionality, consistent with the observation that a G/C range 30%-70% promotes efficient RNAi targeting. Application of this criterion alone provided only a marginal increase in the probability of selecting functional siRNAs from the panel: selection of F50 and F95 siRNAs was improved by 3.6% and 2.2%, respectively. The siRNA panel presented here permitted a more systematic analysis and quantification of the importance of this criterion than that used previously.

A relative measure of local internal stability is the A/U base pair (bp) content; therefore, the frequency of A/U bp was determined for each of the five terminal positions of the duplex (5′ sense (S)/5′ antisense (AS)) of all siRNAs in the panel. Duplexes were then categorized by the number of A/U bp in positions 1-5 and 15-19 of the sense strand. The thermodynamic flexibility of the duplex 5′-end (positions 1-5; S) did not appear to correlate appreciably with silencing potency, while that of the 3′-end (positions 15-19; S) correlated with efficient silencing. No duplexes lacking A/U bp in positions 15-19 were functional. The presence of one A/U bp in this region conferred some degree of functionality, but the presence of three or more A/Us was preferable and therefore defined as Criterion II. When applied to the test panel, only a marginal increase in the probability of functional siRNA selection was achieved: a 1.8% and 2.3% increase for F50 and F95 duplexes, respectively (Table IV).

The complementary strands of siRNAs that contain internal repeats or palindromes may form internal fold-back structures. These hairpin-like structures exist in equilibrium with the duplexed form effectively reducing the concentration of functional duplexes. The propensity to form internal hairpins and their relative stability can be estimated by predicted melting temperatures. High Tm reflects a tendency to form hairpin structures. Lower Tm values indicate a lesser tendency to form hairpins. When the functional classes of siRNAs were sorted by T_(m) (FIG. 3 c), the following trends were identified: duplexes lacking stable internal repeats were the most potent silencers (no F95 duplex with predicted hairpin structure T_(m)>60° C.). In contrast, about 60% of the duplexes in the groups having internal hairpins with calculated T_(m) values less than 20° C. were F80. Thus, the stability of internal repeats is inversely proportional to the silencing effect and defines Criterion III (predicted hairpin structure T_(m)≦20° C.).

Sequence-Based Determinants of siRNA Functionality

When the siRNA panel was sorted into functional and non-functional groups, the frequency of a specific nucleotide at each position in a functional siRNA duplex was compared with that of a nonfunctional duplex in order to assess the preference for or against a certain nucleotide. FIG. 4 shows the results of these queries and the subsequent resorting of the data set (from FIG. 2). The data is separated into two sets: those duplexes that meet the criteria, a specific nucleotide in a certain position—grouped on the left (Selected) and those that do not—grouped on the right (Eliminated). The duplexes are further sorted from most functional to least functional with the y-axis of FIG. 4 a-e representing the % expression i.e., the amount of silencing that is elicited by the duplex (Note: each position on the X-axis represents a different duplex). Statistical analysis revealed correlations between silencing and several sequence-related properties of siRNAs. FIG. 4 and Table IV show quantitative analysis for the following five sequence-related properties of siRNA: (A) an A at position 19 of the sense strand; (B) an A at position 3 of the sense strand; (C) a U at position 10 of the sense strand; (D) a base other than G at position 13 of the sense strand; and (E) a base other than C at position 19 of the sense strand.

When the siRNAs in the panel were evaluated for the presence of an A at position 19 of the sense strand, the percentage of non-functional duplexes decreased from 20% to 11.8%, and the percentage of F95 duplexes increased from 21.7% to 29.4% (Table IV). Thus, the presence of an A in this position defined Criterion IV.

Another sequence-related property correlated with silencing was the presence of an A in position 3 of the sense strand (FIG. 4 b). Of the siRNAs with A3, 34.4% were F95, compared with 21.7% randomly selected siRNAs. The presence of a U base in position 10 of the sense strand exhibited an even greater impact (FIG. 4 c). Of the duplexes in this group, 41.7% were F95. These properties became criteria V and VI, respectively.

Two negative sequence-related criteria that were identified also appear on FIG. 4. The absence of a G at position 13 of the sense strand, conferred a marginal increase in selecting functional duplexes (FIG. 4 d). Similarly, lack of a C at position 19 of the sense strand also correlated with functionality (FIG. 4 e). Thus, among functional duplexes, position 19 was most likely occupied by A, and rarely occupied by C. These rules were defined as criteria VII and VIII, respectively.

Application of each criterion individually provided marginal but statistically significant increases in the probability of selecting a potent siRNA. Although the results were informative, the inventors sought to maximize potency and therefore consider multiple criteria or parameters. Optimization is particularly important when developing therapeutics. Interestingly, the probability of selecting a functional siRNA based on each thermodynamic criteria was 2%-4% higher than random, but 4%-8% higher for the sequence-related determinates. Presumably, these sequence-related increases reflect the complexity of the RNAi mechanism and the multitude of protein-RNA interactions that are involved in RNAi-mediated silencing. TABLE IV PERCENT IMPROVEMENT CRITERION FUNCTIONAL OVER RANDOM (%) I. 30%-52% G/C Content <F50 16.4 −3.6 ≧F50 83.6 3.6 ≧F80 60.4 4.3 ≧F95 23.9 2.2 II. At least 3 A/U bases at <F50 18.2 −1.8 positions 15-19 of the sense ≧F50 81.8 1.8 strand ≧F80 59.7 3.6 ≧F95 24.0 2.3 III. Absence of internal <F50 16.7 −3.3 repeats, as measured by Tm of ≧F50 83.3 3.3 secondary structure ≦20° C. ≧F80 61.1 5.0 ≧F95 24.6 2.9 IV. An A base at position 19 <F50 11.8 −8.2 of the sense strand ≧F50 88.2 8.2 ≧F80 75.0 18.9 ≧F95 29.4 7.7 V. An A base at position 3 of <F50 17.2 −2.8 the sense strand ≧F50 82.8 2.8 ≧F80 62.5 6.4 ≧F95 34.4 12.7 VI. A U base at position 10 <F50 13.9 −6.1 of the sense strand ≧F50 86.1 6.1 ≧F80 69.4 13.3 ≧F95 41.7 20 VII. A base other than C at <F50 18.8 −1.2 position 19 of the sense strand ≧F50 81.2 1.2 ≧F80 59.7 3.6 ≧F95 24.2 2.5 VIII. A base other than G at <F50 15.2 −4.8 position 13 of the sense strand ≧F50 84.8 4.8 ≧F80 61.4 5.3 ≧F95 26.5 4.8 The siRNA Selection Algorithm

In an effort to improve selection further, all identified criteria, including but not limited to those listed in Table IV were combined into the algorithms embodied in Formula VIII, Formula IX, and Formula X. Each siRNA was then assigned a score (referred to as a SMARTSCORE™, or siRNA ranking) according to the values derived from the formulas. Duplexes that scored higher than 0 or −20 (unadjusted), for Formulas VIII and IX, respectively, effectively selected a set of functional siRNAs and excluded all non-functional siRNAs. Conversely, all duplexes scoring lower than 0 and −20 (minus 20) according to formulas VIII and IX, respectively, contained some functional siRNAs but included all non-functional siRNAs. A graphical representation of this selection is shown in FIG. 5. It should be noted that the scores derived from the algorithm can also be provided as “adjusted” scores. To convert Formula VIII unadjusted scores into adjusted scores it is necessary to use the following equation: (160+unadjusted score)/2.25

When this takes place, an unadjusted score of “0” (zero) is converted to 75. Similarly, unadjusted scores for Formula X can be converted to adjusted scores. In this instance, the following equation is applied: (228+unadjusted score)/3.56

When these manipulations take place, an unadjusted score of 38 is converted to an adjusted score of 75.

The methods for obtaining the seven criteria embodied in Table IV are illustrative of the results of the process used to develop the information for Formulas VIII, IX, and X. Thus similar techniques were used to establish the other variables and their multipliers. As described above, basic statistical methods were use to determine the relative values for these multipliers.

To determine the value for “Improvement over Random” the difference in the frequency of a given attribute (e.g., GC content, base preference) at a particular position is determined between individual functional groups (e.g., <F50) and the total siRNA population studied (e.g., 270 siRNA molecules selected randomly). Thus, for instance, in Criterion I (30%-52% GC content) members of the <F50 group were observed to have GC contents between 30-52% in 16.4% of the cases. In contrast, the total group of 270 siRNAs had GC contents in this range, 20% of the time. Thus for this particular attribute, there is a small negative correlation between 30%-52% GC content and this functional group (i.e., 16.4%-20%=−3.6%). Similarly, for Criterion VI, (a “U” at position 10 of the sense strand), the >F95 group contained a “U” at this position 41.7% of the time. In contrast, the total group of 270 siRNAs had a “U” at this position 21.7% of the time, thus the improvement over random is calculated to be 20% (or 41.7%-21.7%).

Identifying the Average Internal Stability Profile of Strong siRNA

In order to identify an internal stability profile that is characteristic of strong siRNA, 270 different siRNAs derived from the cyclophilin B, the diazepam binding inhibitor (DBI), and the luciferase gene were individually transfected into HEK293 cells and tested for their ability to induce RNAi of the respective gene. Based on their performance in the in vivo assay, the sequences were then subdivided into three groups, (i) >95% silencing; (ii) 80-95% silencing; and (iii) less than 50% silencing. Sequences exhibiting 51-84% silencing were eliminated from further consideration to reduce the difficulties in identifying relevant thermodynamic patterns.

Following the division of siRNA into three groups, a statistical analysis was performed on each member of each group to determine the average internal stability profile (AISP) of the siRNA. To accomplish this the Oligo 5.0 Primer Analysis Software and other related statistical packages (e.g., Excel) were exploited to determine the internal stability of pentamers using the nearest neighbor method described by Freier et al., (1986) Improved free-energy parameters for predictions of RNA duplex stability, Proc Natl. Acad. Sci. USA 83(24): 9373-7. Values for each group at each position were then averaged, and the resulting data were graphed on a linear coordinate system with the Y-axis expressing the AG (free energy) values in kcal/mole and the X-axis identifying the position of the base relative to the 5′ end.

The results of the analysis identified multiple key regions in siRNA molecules that were critical for successful gene silencing. At the 3′-most end of the sense strand (5′antisense), highly functional siRNA (>95% gene silencing, see FIG. 6 a, >F95) have a low internal stability (AISP of position 19=˜−7.6 kcal/mol). In contrast low-efficiency siRNA (i.e., those exhibiting less than 50% silencing, <F50) display a distinctly different profile, having high ΔG values (˜−8.4 kcal/mol) for the same position. Moving in a 5′ (sense strand) direction, the internal stability of highly efficient siRNA rises (position 12=˜−8.3 kcal/mole) and then drops again (position 7=˜−7.7 kcal/mol) before leveling off at a value of approximately −8.1 kcal/mol for the 5′ terminus. siRNA with poor silencing capabilities show a distinctly different profile. While the AISP value at position 12 is nearly identical with that of strong siRNAs, the values at positions 7 and 8 rise considerably, peaking at a high of ˜−9.0 kcal/mol. In addition, at the 5′ end of the molecule the AISP profile of strong and weak siRNA differ dramatically. Unlike the relatively strong values exhibited by siRNA in the >95% silencing group, siRNAs that exhibit poor silencing activity have weak AISP values (−7.6, −7.5, and −7.5 kcal/mol for positions 1, 2 and 3 respectively).

Overall the profiles of both strong and weak siRNAs form distinct sinusoidal shapes that are roughly 180° out-of-phase with each other. While these thermodynamic descriptions define the archetypal profile of a strong siRNA, it will likely be the case that neither the ΔG values given for key positions in the profile or the absolute position of the profile along the Y-axis (i.e., the ΔG-axis) are absolutes. Profiles that are shifted upward or downward (i.e., having on an average, higher or lower values at every position) but retain the relative shape and position of the profile along the X-axis can be foreseen as being equally effective as the model profile described here. Moreover, it is likely that siRNA that have strong or even stronger gene-specific silencing effects might have exaggerated ΔG values (either higher or lower) at key positions. Thus, for instance, it is possible that the 5′-most position of the sense strand (position 19) could have ΔG values of 7.4 kcal/mol or lower and still be a strong siRNA if, for instance, a G-C→G-T/U mismatch were substituted at position 19 and altered duplex stability. Similarly, position 12 and position 7 could have values above 8.3 kcal/mol and below 7.7 kcal/mole, respectively, without abating the silencing effectiveness of the molecule. Thus, for instance, at position 12, a stabilizing chemical modification (e.g., a chemical modification of the 2′ position of the sugar backbone) could be added that increases the average internal stability at that position. Similarly, at position 7, mismatches similar to those described previously could be introduced that would lower the AG values at that position.

Lastly, it is important to note that while functional and non-functional siRNA were originally defined as those molecules having specific silencing properties, both broader or more limiting parameters can be used to define these molecules. As used herein, unless otherwise specified, “non-functional siRNA” are defined as those siRNA that induce less than 50% (<50%) target silencing, “semi-functional siRNA” induce 50-79% target silencing, “functional siRNA” are molecules that induce 80-95% gene silencing, and “highly-functional siRNA” are molecules that induce great than 95% gene silencing. These definitions are not intended to be rigid and can vary depending upon the design and needs of the application. For instance, it is possible that a researcher attempting to map a gene to a chromosome using a functional assay, may identify an siRNA that reduces gene activity by only 30%. While this level of gene silencing may be “non-functional” for, e.g., therapeutic needs, it is sufficient for gene mapping purposes and is, under these uses and conditions, “functional.” For these reasons, functional siRNA can be defined as those molecules having greater than 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% silencing capabilities at 100 nM transfection conditions. Similarly, depending upon the needs of the study and/or application, non-functional and semi-functional siRNA can be defined as having different parameters. For instance, semi-functional siRNA can be defined as being those molecules that induce 20%, 30%, 40%, 50%, 60%, or 70% silencing at 100 nM transfection conditions. Similarly, non-functional siRNA can be defined as being those molecules that silence gene expression by less than 70%, 60%, 50%, 40%, 30%, or less. Nonetheless, unless otherwise stated, the descriptions stated in the “Definitions” section of this text should be applied.

Functional attributes can be assigned to each of the key positions in the AISP of strong siRNA. The low 5′ (sense strand) AISP values of strong siRNAs may be necessary for determining which end of the molecule enters the RISC complex. In contrast, the high and low AISP values observed in the central regions of the molecule may be critical for siRNA-target mRNA interactions and product release, respectively.

If the AISP values described above accurately define the thermodynamic parameters of strong siRNA, it would be expected that similar patterns would be observed in strong siRNA isolated from nature. Natural siRNAs exist in a harsh, RNase-rich environment and it can be hypothesized that only those siRNA that exhibit heightened affinity for RISC (i.e., siRNA that exhibit an average internal stability profile similar to those observed in strong siRNA) would survive in an intracellular environment. This hypothesis was tested using GFP-specific siRNA isolated from N. benthamiana. Llave et al. (2002) Endogenous and Silencing-Associated Small RNAs in Plants, The Plant Cell 14, 1605-1619, introduced long double-stranded GFP-encoding RNA into plants and subsequently re-isolated GFP-specific siRNA from the tissues. The AISP of fifty-nine of these GFP-siRNA were determined, averaged, and subsequently plotted alongside the AISP profile obtained from the cyclophilin B/DBI/luciferase siRNA having >90% silencing properties (FIG. 6 b). Comparison of the two groups show that profiles are nearly identical. This finding validates the information provided by the internal stability profiles and demonstrates that: (1) the profile identified by analysis of the cyclophilin B/DBI/luciferase siRNAs are not gene specific; and (2) AISP values can be used to search for strong siRNAs in a variety of species.

Both chemical modifications and base-pair mismatches can be incorporated into siRNA to alter the duplex's AISP and functionality. For instance, introduction of mismatches at positions 1 or 2 of the sense strand destabilized the 5′ end of the sense strand and increases the functionality of the molecule (see Luc, FIG. 7). Similarly, addition of 2′-O-methyl groups to positions 1 and 2 of the sense strand can also alter the AISP and (as a result) increase both the functionality of the molecule and eliminate off-target effects that results from sense strand homology with the unrelated targets (FIG. 8).

Rationale for Criteria in a Biological Context

The fate of siRNA in the RNAi pathway may be described in 5 major steps: (1) duplex recognition and pre-RISC complex formation; (2) ATP-dependent duplex unwinding/strand selection and RISC activation; (3) mRNA target identification; (4) mRNA cleavage, and (5) product release (FIG. 1). Given the level of nucleic acid-protein interactions at each step, siRNA functionality is likely influenced by specific biophysical and molecular properties that promote efficient interactions within the context of the multi-component complexes. Indeed, the systematic analysis of the siRNA test set identified multiple factors that correlate well with functionality. When combined into a single algorithm, they proved to be very effective in selecting active siRNAs.

The factors described here may also be predictive of key functional associations important for each step in RNAi. For example, the potential formation of internal hairpin structures correlated negatively with siRNA functionality. Complementary strands with stable internal repeats are more likely to exist as stable hairpins thus decreasing the effective concentration of the functional duplex form. This suggests that the duplex is the preferred conformation for initial pre-RISC association. Indeed, although single complementary strands can induce gene silencing, the effective concentration required is at least two orders of magnitude higher than that of the duplex form.

siRNA-pre-RISC complex formation is followed by an ATP-dependent duplex unwinding step and “activation” of the RISC. The siRNA functionality was shown to correlate with overall low internal stability of the duplex and low internal stability of the 3′ sense end (or differential internal stability of the 3′ sense compare to the 5′ sense strand), which may reflect strand selection and entry into the RISC. Overall duplex stability and low internal stability at the 3′ end of the sense strand were also correlated with siRNA functionality. Interestingly, siRNAs with very high and very low overall stability profiles correlate strongly with non-functional duplexes. One interpretation is that high internal stability prevents efficient unwinding while very low stability reduces siRNA target affinity and subsequent mRNA cleavage by the RISC.

Several criteria describe base preferences at specific positions of the sense strand and are even more intriguing when considering their potential mechanistic roles in target recognition and mRNA cleavage. Base preferences for A at position 19 of the sense strand but not C, are particularly interesting because they reflect the same base preferences observed for naturally occurring miRNA precursors. That is, among the reported miRNA precursor sequences 75% contain a U at position 1 which corresponds to an A in position 19 of the sense strand of siRNAs, while G was under-represented in this same position for miRNA precursors. These observations support the hypothesis that both miRNA precursors and siRNA duplexes are processed by very similar if not identical protein machinery. The functional interpretation of the predominance of a U/A base pair is that it promotes flexibility at the 5′antisense ends of both siRNA duplexes and miRNA precursors and facilitates efficient unwinding and selective strand entrance into an activated RISC.

Among the criteria associated with base preferences that are likely to influence mRNA cleavage or possibly product release, the preference for U at position 10 of the sense strand exhibited the greatest impact, enhancing the probability of selecting an F80 sequence by 13.3%. Activated RISC preferentially cleaves target mRNA between nucleotides 10 and 11 relative to the 5′ end of the complementary targeting strand. Therefore, it may be that U, the preferred base for most endoribonucleases, at this position supports more efficient cleavage. Alternatively, a U/A bp between the targeting siRNA strand and its cognate target mRNA may create an optimal conformation for the RISC-associated “slicing” activity.

Post Algorithm Filters

According to another embodiment, the output of any one of the formulas previously listed can be filtered to remove or select for siRNAs containing undesirable or desirable motifs or properties, respectively. In one example, sequences identified by any of the formulas can be filtered to remove any and all sequences that induce toxicity or cellular stress. Introduction of an siRNA containing a toxic motif into a cell can induce cellular stress and/or cell death (apoptosis) which in turn can mislead researchers into associating a particular (e.g., nonessential) gene with, e.g., an essential function. Alternatively, sequences generated by any of the before mentioned formulas can be filtered to identify and retain duplexes that contain toxic motifs. Such duplexes may be valuable from a variety of perspectives including, for instance, uses as therapeutic molecules. A variety of toxic motifs exist and can exert their influence on the cell through RNAi and non-RNAi pathways. Examples of toxic motifs are explained more fully in commonly assigned U.S. Provisional Patent Application Ser. No. 60/538,874, entitled “Identification of Toxic Sequences,” filed Jan. 23, 2004. Briefly, toxic motifs include A/G UUU A/G/U, G/C AAA G/C, and GCCA, or a complement of any of the foregoing.

In another instance, sequences identified by any of the before mentioned formulas can be filtered to identify duplexes that contain motifs (or general properties) that provide serum stability or induce serum instability. In one envisioned application of siRNA as therapeutic molecules, duplexes targeting disease-associated genes will be introduced into patients intravenously. As the half-life of single and double stranded RNA in serum is short, post-algorithm filters designed to select molecules that contain motifs that enhance duplex stability in the presence of serum and/or (conversely) eliminate duplexes that contain motifs that destabilize siRNA in the presence of serum, would be beneficial.

In another instance, sequences identified by any of the before mentioned formulas can be filtered to identify duplexes that are hyperfunctional. Hyperfunctional sequences are defined as those sequences that (1) induce greater than 95% silencing of a specific target when they are transfected at subnanomolar concentrations (i.e., less than one nanomolar); and/or (2) induce functional (or better) levels of silencing for greater than 96 hours. Filters that identify hyperfunctional molecules can vary widely. In one example, the top ten, twenty, thirty, or forty siRNA can be assessed for the ability to silence a given target at, e.g., concentrations of 1 nM and 0.5 nM to identify hyperfunctional molecules.

Pooling

According to another embodiment, the present invention provides a pool of at least two siRNAs, preferably in the form of a kit or therapeutic reagent, wherein one strand of each of the siRNAs, the sense strand comprises a sequence that is substantially similar to a sequence within a target mRNA. The opposite strand, the antisense strand, will preferably comprise a sequence that is substantially complementary to that of the target mRNA. More preferably, one strand of each siRNA will comprise a sequence that is identical to a sequence that is contained in the target mRNA. Most preferably, each siRNA will be 19 base pairs in length, and one strand of each of the siRNAs will be 100% complementary to a portion of the target mRNA.

By increasing the number of siRNAs directed to a particular target using a pool or kit, one is able both to increase the likelihood that at least one siRNA with satisfactory functionality will be included, as well as to benefit from additive or synergistic effects. Further, when two or more siRNAs directed against a single gene do not have satisfactory levels of functionality alone, if combined, they may satisfactorily promote degradation of the target messenger RNA and successfully inhibit translation. By including multiple siRNAs in the system, not only is the probability of silencing increased, but the economics of operation are also improved when compared to adding different siRNAs sequentially. This effect is contrary to the conventional wisdom that the concurrent use of multiple siRNA will negatively impact gene silencing (e.g., Holen, T. et al. (2003) Similar behavior of single strand and double strand siRNAs suggests they act through a common RNAi pathway. NAR 31: 2401-21407).

In fact, when two siRNAs were pooled together, 54% of the pools of two siRNAs induced more than 95% gene silencing. Thus, a 2.5-fold increase in the percentage of functionality was achieved by randomly combining two siRNAs. Further, over 84% of pools containing two siRNAs induced more than 80% gene silencing.

More preferably, the kit is comprised of at least three siRNAs, wherein one strand of each siRNA comprises a sequence that is substantially similar to a sequence of the target mRNA and the other strand comprises a sequence that is substantially complementary to the region of the target mRNA. As with the kit that comprises at least two siRNAs, more preferably one strand will comprise a sequence that is identical to a sequence that is contained in the mRNA and another strand that is 100% complementary to a sequence that is contained in the mRNA. During experiments, when three siRNAs were combined together, 60% of the pools induced more than 95% gene silencing and 92% of the pools induced more than 80% gene silencing.

Further, even more preferably, the kit is comprised of at least four siRNAs, wherein one strand of each siRNA comprises a sequence that is substantially similar to a region of the sequence of the target mRNA, and the other strand comprises a sequence that is substantially complementary to the region of the target mRNA. As with the kit or pool that comprises at least two siRNAs, more preferably one strand of each of the siRNA duplexes will comprise a sequence that is identical to a sequence that is contained in the mRNA, and another strand that is 100% complementary to a sequence that is contained in the mRNA.

Additionally, kits and pools with at least five, at least six, and at least seven siRNAs may also be useful with the present invention. For example, pools of five siRNA induced 95% gene silencing with 77% probability and 80% silencing with 98.8% probability. Thus, pooling of siRNAs together can result in the creation of a target-specific silencing reagent with almost a 99% probability of being functional. The fact that such high levels of success are achievable using such pools of siRNA, enables one to dispense with costly and time-consuming target-specific validation procedures.

For this embodiment, as well as the other aforementioned embodiments, each of the siRNAs within a pool will preferably comprise 18-30 base pairs, more preferably 18-25 base pairs, and most preferably 19 base pairs. Within each siRNA, preferably at least 18 contiguous bases of the antisense strand will be 100% complementary to the target mRNA. More preferably, at least 19 contiguous bases of the antisense strand will be 100% complementary to the target mRNA. Additionally, there may be overhangs on either the sense strand or the antisense strand, and these overhangs may be at either the 5′ end or the 3′ end of either of the strands, for example there may be one or more overhangs of 1-6 bases. When overhangs are present, they are not included in the calculation of the number of base pairs. The two nucleotide 3′ overhangs mimic natural siRNAs and are commonly used but are not essential. Preferably, the overhangs should consist of two nucleotides, most often dTdT or UU at the 3′ end of the sense and antisense strand that are not complementary to the target sequence. The siRNAs may be produced by any method that is now known or that comes to be known for synthesizing double stranded RNA that one skilled in the art would appreciate would be useful in the present invention. Preferably, the siRNAs will be produced by Dharmacon's proprietary ACE® technology. However, other methods for synthesizing siRNAs are well known to persons skilled in the art and include, but are not limited to, any chemical synthesis of RNA oligonucleotides, ligation of shorter oligonucleotides, in vitro transcription of RNA oligonucleotides, the use of vectors for expression within cells, recombinant Dicer products and PCR products.

The siRNA duplexes within the aforementioned pools of siRNAs may correspond to overlapping sequences within a particular mRNA, or non-overlapping sequences of the mRNA. However, preferably they correspond to non-overlapping sequences. Further, each siRNA may be selected randomly, or one or more of the siRNA may be selected according to the criteria discussed above for maximizing the effectiveness of siRNA.

Included in the definition of siRNAs are siRNAs that contain substituted and/or labeled nucleotides that may, for example, be labeled by radioactivity, fluorescence or mass. The most common substitutions are at the 2′ position of the ribose sugar, where moieties such as H (hydrogen) F, NH₃, OCH₃ and other O— alkyl, alkenyl, alkynyl, and orthoesters, may be substituted, or in the phosphorous backbone, where sulfur, amines or hydrocarbons may be substituted for the bridging of non-bridging atoms in the phosphodiester bond. Examples of modified siRNAs are explained more fully in commonly assigned U.S. patent application Ser. No. 10/613,077, filed Jul. 1, 2003.

Additionally, as noted above, the cell type into which the siRNA is introduced may affect the ability of the siRNA to enter the cell; however, it does not appear to affect the ability of the siRNA to function once it enters the cell. Methods for introducing double-stranded RNA into various cell types are well known to persons skilled in the art.

As persons skilled in the art are aware, in certain species, the presence of proteins such as RdRP, the RNA-dependent RNA polymerase, may catalytically enhance the activity of the siRNA. For example, RdRP propagates the RNAi effect in C. elegans and other non-mammalian organisms. In fact, in organisms that contain these proteins, the siRNA may be inherited. Two other proteins that are well studied and known to be a part of the machinery are members of the Argonaute family and Dicer, as well as their homologues. There is also initial evidence that the RISC complex might be associated with the ribosome so the more efficiently translated mRNAs will be more susceptible to silencing than others.

Another very important factor in the efficacy of siRNA is mRNA localization. In general, only cytoplasmic mRNAs are considered to be accessible to RNAi to any appreciable degree. However, appropriately designed siRNAs, for example, siRNAs modified with internucleotide linkages or 2′-O-methyl groups, may be able to cause silencing by acting in the nucleus. Examples of these types of modifications are described in commonly assigned U.S. patent application Ser. Nos. 10/431,027 and 10/613,077.

As described above, even when one selects at least two siRNAs at random, the effectiveness of the two may be greater than one would predict based on the effectiveness of two individual siRNAs. This additive or synergistic effect is particularly noticeable as one increases to at least three siRNAs, and even more noticeable as one moves to at least four siRNAs. Surprisingly, the pooling of the non-functional and semi-functional siRNAs, particularly more than five siRNAs, can lead to a silencing mixture that is as effective if not more effective than any one particular functional siRNA.

Within the kits of the present invention, preferably each siRNA will be present in a concentration of between 0.001 and 200 μM, more preferably between 0.01 and 200 nM, and most preferably between 0.1 and 10 nM.

In addition to preferably comprising at least four or five siRNAs, the kits of the present invention will also preferably comprise a buffer to keep the siRNA duplex stable. Persons skilled in the art are aware of buffers suitable for keeping siRNA stable. For example, the buffer may be comprised of 100 mM KCl, 30 mM HEPES-pH 7.5, and 1 mM MgCl₂. Alternatively, kits might contain complementary strands that contain any one of a number of chemical modifications (e.g., a 2′-O-ACE) that protect the agents from degradation by nucleases. In this instance, the user may (or may not) remove the modifying protective group (e.g., deprotect) before annealing the two complementary strands together.

By way of example, the kits may be organized such that pools of siRNA duplexes are provided on an array or microarray of wells or drops for a particular gene set or for unrelated genes. The array may, for example, be in 96 wells, 384 wells or 1284 wells arrayed in a plastic plate or on a glass slide using techniques now known or that come to be known to persons skilled in the art. Within an array, preferably there will be controls such as functional anti-lamin A/C, cyclophilin and two siRNA duplexes that are not specific to the gene of interest.

In order to ensure stability of the siRNA pools prior to usage, they may be retained in lyophilized form at minus twenty degrees (−20° C.) until they are ready for use. Prior to usage, they should be resuspended; however, even once resuspended, for example, in the aforementioned buffer, they should be kept at minus twenty degrees, (−20° C.) until used. The aforementioned buffer, prior to use, may be stored at approximately 4° C. or room temperature. Effective temperatures at which to conduct transfections are well known to persons skilled in the art and include for example, room temperature.

The kits may be applied either in vivo or in vitro. Preferably, the siRNA of the pools or kits is applied to a cell through transfection, employing standard transfection protocols. These methods are well known to persons skilled in the art and include the use of lipid-based carriers, electroporation, cationic carriers, and microinjection. Further, one could apply the present invention by synthesizing equivalent DNA sequences (either as two separate, complementary strands, or as hairpin molecules) instead of siRNA sequences and introducing them into cells through vectors. Once in the cells, the cloned DNA could be transcribed, thereby forcing the cells to generate the siRNA. Examples of vectors suitable for use with the present application include but are not limited to the standard transient expression vectors, adenoviruses, retroviruses, lentivirus-based vectors, as well as other traditional expression vectors. Any vector that has an adequate siRNA expression and procession module may be used. Furthermore, certain chemical modifications to siRNAs, including but not limited to conjugations to other molecules, may be used to facilitate delivery. For certain applications it may be preferable to deliver molecules without transfection by simply formulating in a physiological acceptable solution.

This embodiment may be used in connection with any of the aforementioned embodiments. Accordingly, the sequences within any pool may be selected by rational design.

Multigene Silencing

In addition to developing kits that contain multiple siRNA directed against a single gene, another embodiment includes the use of multiple siRNA targeting multiple genes. Multiple genes may be targeted through the use of high- or hyper-functional siRNA. High- or hyper-functional siRNA that exhibit increased potency, require lower concentrations to induce desired phenotypic (and thus therapeutic) effects. This circumvents RISC saturation. It therefore reasons that if lower concentrations of a single siRNA are needed for knockout or knockdown expression of one gene, then the remaining (uncomplexed) RISC will be free and available to interact with siRNA directed against two, three, four, or more, genes. Thus in this embodiment, the authors describe the use of highly functional or hyper-functional siRNA to knock out three separate genes. More preferably, such reagents could be combined to knockout four distinct genes. Even more preferably, highly functional or hyperfunctional siRNA could be used to knock out five distinct genes. Most preferably, siRNA of this type could be used to knockout or knockdown the expression of six or more genes.

Hyperfunctional siRNA

The term hyperfunctional siRNA (hf-siRNA) describes a subset of the siRNA population that induces RNAi in cells at low- or sub-nanomolar concentrations for extended periods of time. These traits, heightened potency and extended longevity of the RNAi phenotype, are highly attractive from a therapeutic standpoint. Agents having higher potency require lesser amounts of the molecule to achieve the desired physiological response, thus reducing the probability of side effects due to “off-target” interference. In addition to the potential therapeutic benefits associated with hyperfunctional siRNA, hf-siRNA are also desirable from an economic perspective. Hyperfunctional siRNA may cost less on a per-treatment basis, thus reducing overall expenditures to both the manufacturer and the consumer.

Identification of hyperfunctional siRNA involves multiple steps that are designed to examine an individual siRNA agent's concentration- and/or longevity-profiles. In one non-limiting example, a population of siRNA directed against a single gene are first analyzed using the previously described algorithm (Formula VIII). Individual siRNA are then introduced into a test cell line and assessed for the ability to degrade the target mRNA. It is important to note that when performing this step it is not necessary to test all of the siRNA. Instead, it is sufficient to test only those siRNA having the highest SMARTSCORES™, or siRNA ranking (i.e., SMARTSCORES™, or siRNA ranking >−10). Subsequently, the gene silencing data is plotted against the SMARTSCORES™, or siRNA rankings (see FIG. 9). siRNA that (1) induce a high degree of gene silencing (i.e., they induce greater than 80% gene knockdown) and (2) have superior SMARTSCORES™ (i.e., a SMARTSCORE™, or siRNA ranking, of >−10, suggesting a desirable average internal stability profile) are selected for further investigations designed to better understand the molecule's potency and longevity. In one, non-limiting study dedicated to understanding a molecule's potency, an siRNA is introduced into one (or more) cell types in increasingly diminishing concentrations (e.g., 3.0→0.3 nM). Subsequently, the level of gene silencing induced by each concentration is examined and siRNA that exhibit hyperfunctional potency (i.e., those that induce 80% silencing or greater at, e.g., picomolar concentrations) are identified. In a second study, the longevity profiles of siRNA having high (>−10) SMARTSCORES™, or siRNA rankings and greater than 80% silencing are examined. In one non-limiting example of how this is achieved, siRNA are introduced into a test cell line and the levels of RNAi are measured over an extended period of time (e.g., 24-168 hrs). siRNAs that exhibit strong RNA interference patterns (i.e., >80% interference) for periods of time greater than, e.g., 120 hours, are thus identified. Studies similar to those described above can be performed on any and all of the >10⁶ siRNA included in this document to further define the most functional molecule for any given gene. Molecules possessing one or both properties (extended longevity and heightened potency) are labeled “hyperfunctional siRNA,” and earmarked as candidates for future therapeutic studies.

While the example(s) given above describe one means by which hyperfunctional siRNA can be isolated, neither the assays themselves nor the selection parameters used are rigid and can vary with each family of siRNA. Families of siRNA include siRNAs directed against a single gene, or directed against a related family of genes.

The highest quality siRNA achievable for any given gene may vary considerably. Thus, for example, in the case of one gene (gene X), rigorous studies such as those described above may enable the identification of an siRNA that, at picomolar concentrations, induces 99⁺% silencing for a period of 10 days. Yet identical studies of a second gene (gene Y) may yield an siRNA that at high nanomolar concentrations (e.g., 100 nM) induces only 75% silencing for a period of 2 days. Both molecules represent the very optimum siRNA for their respective gene targets and therefore are designated “hyperfunctional.” Yet due to a variety of factors including but not limited to target concentration, siRNA stability, cell type, off-target interference, and others, equivalent levels of potency and longevity are not achievable. Thus, for these reasons, the parameters described in the before mentioned assays can vary. While the initial screen selected siRNA that had SMARTSCORES™ above −10 and a gene silencing capability of greater than 80%, selections that have stronger (or weaker) parameters can be implemented. Similarly, in the subsequent studies designed to identify molecules with high potency and longevity, the desired cutoff criteria (i.e., the lowest concentration that induces a desirable level of interference, or the longest period of time that interference can be observed) can vary. The experimentation subsequent to application of the rational criteria of this application is significantly reduced where one is trying to obtain a suitable hyperfunctional siRNA for, for example, therapeutic use. When, for example, the additional experimentation of the type described herein is applied by one skilled in the art with this disclosure in hand, a hyperfunctional siRNA is readily identified.

The siRNA may be introduced into a cell by any method that is now known or that comes to be known and that from reading this disclosure, persons skilled in the art would determine would be useful in connection with the present invention in enabling siRNA to cross the cellular membrane. These methods include, but are not limited to, any manner of transfection, such as, for example, transfection employing DEAE-Dextran, calcium phosphate, cationic lipids/liposomes, micelles, manipulation of pressure, microinjection, electroporation, immunoporation, use of vectors such as viruses, plasmids, cosmids, bacteriophages, cell fusions, and coupling of the polynucleotides to specific conjugates or ligands such as antibodies, antigens, or receptors, passive introduction, adding moieties to the siRNA that facilitate its uptake, and the like.

Having described the invention with a degree of particularity, examples will now be provided. These examples are not intended to and should not be construed to limit the scope of the claims in any way.

EXAMPLES General Techniques and Nomenclatures

siRNA nomenclature. All siRNA duplexes are referred to by sense strand. The first nucleotide of the 5′-end of the sense strand is position 1, which corresponds to position 19 of the antisense strand for a 19-mer. In most cases, to compare results from different experiments, silencing was determined by measuring specific transcript mRNA levels or enzymatic activity associated with specific transcript levels, 24 hours post-transfection, with siRNA concentrations held constant at 100 nM. For all experiments, unless otherwise specified, transfection efficiency was ensured to be over 95%, and no detectable cellular toxicity was observed. The following system of nomenclature was used to compare and report siRNA-silencing functionality: “F” followed by the degree of minimal knockdown. For example, F50 signifies at least 50% knockdown, F80 means at least 80%, and so forth. For this study, all sub-F50 siRNAs were considered non-functional.

Cell culture and transfection. 96-well plates are coated with 50 μl of 50 mg/ml poly-L-lysine (Sigma) for 1 hr, and then washed 3× with distilled water before being dried for 20 min. HEK293 cells or HEK293Lucs or any other cell type of interest are released from their solid support by trypsinization, diluted to 3.5×10⁵ cells/ml, followed by the addition of 100 μL of cells/well. Plates are then incubated overnight at 37° C., 5% CO₂. Transfection procedures can vary widely depending on the cell type and transfection reagents. In one non-limiting example, a transfection mixture consisting of 2 mL Opti-MEM I (Gibco-BRL), 80 μl Lipofectamine 2000 (Invitrogen), 15 μL SUPERNasin at 20 U/R1 (Ambion), and 1.5 μl of reporter gene plasmid at 1 μg/μl is prepared in 5-ml polystyrene round bottom tubes. One hundred μl of transfection reagent is then combined with 100 μl of siRNAs in polystyrene deep-well titer plates (Beckman) and incubated for 20 to 30 min at room temperature. Five hundred and fifty microliters of Opti-MEM is then added to each well to bring the final siRNA concentration to 100 nM. Plates are then sealed with parafilm and mixed. Media is removed from HEK293 cells and replaced with 95 μl of transfection mixture. Cells are incubated overnight at 37° C., 5% CO₂.

Quantification of gene knockdown. A variety of quantification procedures can be used to measure the level of silencing induced by siRNA or siRNA pools. In one non-limiting example: to measure mRNA levels 24 hrs post-transfection, QuantiGene branched-DNA (bDNA) kits (Bayer) (Wang, et al, Regulation of insulin preRNA splicing by glucose. Proc. Natl. Acad. Sci. USA 1997, 94:4360.) are used according to manufacturer instructions. To measure luciferase activity, media is removed from HEK293 cells 24 hrs post-transfection, and 50 μl of Steady-GLO reagent (Promega) is added. After 5 minutes, plates are analyzed on a plate reader.

Example I Sequences Used to Develop the Algorithm

Anti-Firefly and anti-Cyclophilin siRNAs panels (FIG. 5 a, b) sorted according to using Formula VIII predicted values. All siRNAs scoring more than 0 (formula VIII) and more then 20 (formula IX) are fully functional. All ninety sequences for each gene (and DBI) appear below in Table III. TABLE III Cyclo 1 SEQ. ID 0032 GUUCCAAAAACAGUGGAUA Cyclo 2 SEQ. ID 0033 UCCAAAAACAGUGGAUAAU Cyclo 3 SEQ. ID 0034 CAAAAACAGUGGAUAAUUU Cyclo 4 SEQ. ID 0035 AAAACAGUGGAUAAUUUUG Cyclo 5 SEQ. ID 0036 AACAGUGGAUAAUUUUGUG Cyclo 6 SEQ. ID 0037 CAGUGGAUAAUUUUGUGGC Cyclo 7 SEQ. ID 0038 GUGGAUAAUUUUGUGGCCU Cyclo 8 SEQ. ID 0039 GGAUAAUUUUGUGGCCUUA Cyclo 9 SEQ. ID 0040 AUAAUUUUGUGGCCUUAGC Cyclo 10 SEQ. ID 0041 AAUUUUGUGGCCUUAGCUA Cyclo 11 SEQ. ID 0042 UUUUGUGGCCUUAGCUACA Cyclo 12 SEQ. ID 0043 UUGUGGCCUUAGCUACAGG Cyclo 13 SEQ. ID 0044 GUGGCCUUAGCUACAGGAG Cyclo 14 SEQ. ID 0045 GGCCUUAGCUACAGGAGAG Cyclo 15 SEQ. ID 0046 CCUUAGCUACAGGAGAGAA Cyclo 16 SEQ. ID 0047 UUAGCUACAGGAGAGAAAG Cyclo 17 SEQ. ID 0048 AGCUACAGGAGAGAAAGGA Cyclo 18 SEQ. ID 0049 CUACAGGAGAGAAAGGAUU Cyclo 19 SEQ. ID 0050 ACAGGAGAGAAAGGAUUUG Cyclo 20 SEQ. ID 0051 AGGAGAGAAAGGAUUUGGC Cyclo 21 SEQ. ID 0052 GAGAGAAAGGAUUUGGCUA Cyclo 22 SEQ. ID 0053 GAGAAAGGAUUUGGCUACA Cyclo 23 SEQ. ID 0054 GAAAGGAUUUGGCUACAAA Cyclo 24 SEQ. ID 0055 AAGGAUUUGGCUACAAAAA Cyclo 25 SEQ. ID 0056 GGAUUUGGCUACAAAAACA Cyclo 26 SEQ. ID 0057 AUUUGGCUACAAAAACAGC Cyclo 27 SEQ. ID 0058 UUGGCUACAAAAACAGCAA Cyclo 28 SEQ. ID 0059 GGCUACAAAAACAGCAAAU Cyclo 29 SEQ. ID 0060 CUACAAAAACAGCAAAUUC Cyclo 30 SEQ. ID 0061 ACAAAAACAGCAAAUUCCA Cyclo 31 SEQ. ID 0062 AAAAACAGCAAAUUCCAUC Cyclo 32 SEQ. ID 0063 AAACAGCAAAUUCCAUCGU Cyclo 33 SEQ. ID 0064 ACAGCAAAUUCCAUCGUGU Cyclo 34 SEQ. ID 0065 AGCAAAUUCCAUCGUGUAA Cyclo 35 SEQ. ID 0066 CAAAUUCCAUCGUGUAAUC Cyclo 36 SEQ. ID 0067 AAUUCCAUCGUGUAAUCAA Cyclo 37 SEQ. ID 0068 UUCCAUCGUGUAAUCAAGG Cyclo 38 SEQ. ID 0069 CCAUCGUGUAAUCAAGGAC Cyclo 39 SEQ. ID 0070 AUCGUGUAAUCAAGGACUU Cyclo 40 SEQ. ID 0071 CGUGUAAUCAAGGACUUCA Cyclo 41 SEQ. ID 0072 UGUAAUCAAGGACUUCAUG Cyclo 42 SEQ. ID 0073 UAAUCAAGGACUUCAUGAU Cyclo 43 SEQ. ID 0074 AUCAAGGACUUCAUGAUCC Cyclo 44 SEQ. ID 0075 CAAGGACUUCAUGAUCCAG Cyclo 45 SEQ. ID 0076 AGGACUUCAUGAUCCAGGG Cyclo 46 SEQ. ID 0077 GACUUCAUGAUCCAGGGCG Cyclo 47 SEQ. ID 0078 CUUCAUGAUCCAGGGCGGA Cyclo 48 SEQ. ID 0079 UCAUGAUCCAGGGCGGAGA Cyclo 49 SEQ. ID 0080 AUGAUCCAGGGCGGAGACU Cyclo 50 SEQ. ID 0081 GAUCCAGGGCGGAGACUUC Cyclo 51 SEQ. ID 0082 UCCAGGGCGGAGACUUCAC Cyclo 52 SEQ. ID 0083 CAGGGCGGAGACUUCACCA Cyclo 53 SEQ. ID 0084 GGGCGGAGACUUCACCAGG Cyclo 54 SEQ. ID 0085 GCGGAGACUUCACCAGGGG Cyclo 55 SEQ. ID 0086 GGAGACUUCACCAGGGGAG Cyclo 56 SEQ. ID 0087 AGACUUCACCAGGGGAGAU Cyclo 57 SEQ. ID 0088 ACUUCACCAGGGGAGAUGG Cyclo 58 SEQ. ID 0089 UUCACCAGGGGAGAUGGCA Cyclo 59 SEQ. ID 0090 CACCAGGGGAGAUGGCACA Cyclo 60 SEQ. ID 0091 CCAGGGGAGAUGGCACAGG Cyclo 61 SEQ. ID 0092 AGGGGAGAUGGCACAGGAG Cyclo 62 SEQ. ID 0093 GGGAGAUGGCACAGGAGGA Cyclo 63 SEQ. ID 0094 GAGAUGGCACAGGAGGAAA Cyclo 64 SEQ. ID 0095 GAUGGCACAGGAGGAAAGA Cyclo 65 SEQ. ID 0096 UGGCACAGGAGGAAAGAGC Cyclo 66 SEQ. ID 0097 GCACAGGAGGAAAGAGCAU Cyclo 67 SEQ. ID 0098 ACAGGAGGAAAGAGCAUCU Cyclo 68 SEQ. ID 0099 AGGAGGAAAGAGCAUCUAC Cyclo 69 SEQ. ID 0100 GAGGAAAGAGCAUCUACGG Cyclo 70 SEQ. ID 0101 GGAAAGAGCAUCUACGGUG Cyclo 71 SEQ. ID 0102 AAAGAGCAUCUACGGUGAG Cyclo 72 SEQ. ID 0103 AGAGCAUCUACGGUGAGCG Cyclo 73 SEQ. ID 0104 AGCAUCUACGGUGAGCGCU Cyclo 74 SEQ. ID 0105 CAUCUACGGUGAGCGCUUC Cyclo 75 SEQ. ID 0106 UCUACGGUGAGCGCUUCCC Cyclo 76 SEQ. ID 0107 UACGGUGAGCGCUUCCCCG Cyclo 77 SEQ. ID 0108 CGGUGAGCGCUUCCCCGAU Cyclo 78 SEQ. ID 0109 GUGAGCGCUUCCCCGAUGA Cyclo 79 SEQ. ID 0110 GAGCGCUUCCCCGAUGAGA Cyclo 80 SEQ. ID 0111 GCGCUUCCCCGAUGAGAAC Cyclo 81 SEQ. ID 0112 GCUUCCCCGAUGAGAACUU Cyclo 82 SEQ. ID 0113 UUCCCCGAUGAGAACUUCA Cyclo 83 SEQ. ID 0114 CCCCGAUGAGAACUUCAAA Cyclo 84 SEQ. ID 0115 CCGAUGAGAACUUCAAACU Cyclo 85 SEQ. ID 0116 GAUGAGAACUUCAAACUGA Cyclo 86 SEQ. ID 0117 UGAGAACUUCAAACUGAAG Cyclo 87 SEQ. ID 0118 AGAACUUCAAACUGAAGCA Cyclo 88 SEQ. ID 0119 AACUUCAAACUGAAGCACU Cyclo 89 SEQ. ID 0120 CUUCAAACUGAAGCACUAC Cyclo 90 SEQ. ID 0121 UCAAACUGAAGCACUACGG DB 1 SEQ. ID 0122 ACGGGCAAGGCCAAGUGGG DB 2 SEQ. ID 0123 CGGGCAAGGCCAAGUGGGA DB 3 SEQ. ID 0124 GGGCAAGGCCAAGUGGGAU DB 4 SEQ. ID 0125 GGCAAGGCCAAGUGGGAUG DB 5 SEQ. ID 0126 GCAAGGCCAAGUGGGAUGC DB 6 SEQ. ID 0127 CAAGGCCAAGUGGGAUGCC DB 7 SEQ. ID 0128 AAGGCCAAGUGGGAUGCCU DB 8 SEQ. ID 0129 AGGCCAAGUGGGAUGCCUG DB 9 SEQ. ID 0130 GGCCAAGUGGGAUGCCUGG DB 10 SEQ. ID 0131 GCCAAGUGGGAUGCCUGGA DB 11 SEQ. ID 0132 CCAAGUGGGAUGCCUGGAA DB 12 SEQ. ID 0133 CAAGUGGGAUGCCUGGAAU DB 13 SEQ. ID 0134 AAGUGGGAUGCCUGGAAUG DB 14 SEQ. ID 0135 AGUGGGAUGCCUGGAAUGA DB 15 SEQ. ID 0136 GUGGGAUGCCUGGAAUGAG DB 16 SEQ. ID 0137 UGGGAUGCCUGGAAUGAGC DB 17 SEQ. ID 0138 GGGAUGCCUGGAAUGAGCU DB 18 SEQ. ID 0139 GGAUGCCUGGAAUGAGCUG DB 19 SEQ. ID 0140 GAUGCCUGGAAUGAGCUGA DB 20 SEQ. ID 0141 AUGCCUGGAAUGAGCUGAA DB 21 SEQ. ID 0142 UGCCUGGAAUGAGCUGAAA DB 22 SEQ. ID 0143 GCCUGGAAUGAGCUGAAAG DB 23 SEQ. ID 0144 CCUGGAAUGAGCUGAAAGG DB 24 SEQ. ID 0145 CUGGAAUGAGCUGAAAGGG DB 25 SEQ. ID 0146 UGGAAUGAGCUGAAAGGGA DB 26 SEQ. ID 0147 GGAAUGAGCUGAAAGGGAC DB 27 SEQ. ID 0148 GAAUGAGCUGAAAGGGACU DB 28 SEQ. ID 0149 AAUGAGCUGAAAGGGACUU DB 29 SEQ. ID 0150 AUGAGCUGAAAGGGACUUC DB 30 SEQ. ID 0151 UGAGCUGAAAGGGACUUCC DB 31 SEQ. ID 0152 GAGCUGAAAGGGACUUCCA DB 32 SEQ. ID 0153 AGCUGAAAGGGACUUCCAA DB 33 SEQ. ID 0154 GCUGAAAGGGACUUCCAAG DB 34 SEQ. ID 0155 CUGAAAGGGACUUCCAAGG DB 35 SEQ. ID 0156 UGAAAGGGACUUCCAAGGA DB 36 SEQ. ID 0157 GAAAGGGACUUCCAAGGAA DB 37 SEQ. ID 0158 AAAGGGACUUCCAAGGAAG DB 38 SEQ. ID 0159 AAGGGACUUCCAAGGAAGA DB 39 SEQ. ID 0160 AGGGACUUCCAAGGAAGAU DB 40 SEQ. ID 0161 GGGACUUCCAAGGAAGAUG DB 41 SEQ. ID 0162 GGACUUCCAAGGAAGAUGC DB 42 SEQ. ID 0163 GACUUCCAAGGAAGAUGCC DB 43 SEQ. ID 0164 ACUUCCAAGGAAGAUGCCA DB 44 SEQ. ID 0165 CUUCCAAGGAAGAUGCCAU DB 45 SEQ. ID 0166 UUCCAAGGAAGAUGCCAUG DB 46 SEQ. ID 0167 UCCAAGGAAGAUGCCAUGA DB 47 SEQ. ID 0168 CCAAGGAAGAUGCCAUGAA DB 48 SEQ. ID 0169 CAAGGAAGAUGCCAUGAAA DB 49 SEQ. ID 0170 AAGGAAGAUGCCAUGAAAG DB 50 SEQ. ID 0171 AGGAAGAUGCCAUGAAAGC DB 51 SEQ. ID 0172 CGAAGAUGCCAUGAAAGCU DB 52 SEQ. ID 0173 GAAGAUGCCAUGAAAGCUU DB 53 SEQ. ID 0174 AAGAUGCCAUGAAAGCUUA DB 54 SEQ. ID 0175 AGAUGCCAUGAAAGCUUAC DB 55 SEQ. ID 0176 GAUGCCAUGAAAGCUUACA DB 56 SEQ. ID 0177 AUGCCAUGAAAGCUUACAU DB 57 SEQ. ID 0178 UGCCAUGAAAGCUUACAUC DB 58 SEQ. ID 0179 GCCAUGAAAGCUUACAUCA DB 59 SEQ. ID 0180 CCAUGAAAGCUUACAUCAA DB 60 SEQ. ID 0181 CAUGAAAGCUUACAUCAAC DB 61 SEQ. ID 0182 AUGAAAGCUUACAUCAACA DB 62 SEQ. ID 0183 UGAAAGCUUACAUCAACAA DB 63 SEQ. ID 0184 GAAAGCUUACAUCAACAAA DB 64 SEQ. ID 0185 AAAGCUUACAUCAACAAAG DB 65 SEQ. ID 0186 AAGCUUACAUCAACAAAGU DB 66 SEQ. ID 0187 AGCUUACAUCAACAAAGUA DB 67 SEQ. ID 0188 GCUUACAUCAACAAAGUAG DB 68 SEQ. ID 0189 CUUACAUCAACAAAGUAGA DB 69 SEQ. ID 0190 UUACAUCAACAAAGUAGAA DB 70 SEQ. ID 0191 UACAUCAACAAAGUAGAAG DB 71 SEQ. ID 0192 ACAUCAACAAAGUAGAAGA DB 72 SEQ. ID 0193 CAUCAACAAAGUAGAAGAG DB 73 SEQ. ID 0194 AUCAACAAAGUAGAAGAGC DB 74 SEQ. ID 0195 UCAACAAAGUAGAAGAGCU DB 75 SEQ. ID 0196 CAACAAAGUAGAAGAGCUA DB 76 SEQ. ID 0197 AACAAAGUAGAAGAGCUAA DB 77 SEQ. ID 0198 ACAAAGUAGAAGAGCUAAA DB 78 SEQ. ID 0199 CAAAGUAGAAGAGCUAAAG DB 79 SEQ. ID 0200 AAAGUAGAAGAGCUAAAGA DB 80 SEQ. ID 0201 AAGUAGAAGAGCUAAAGAA DB 81 SEQ. ID 0202 AGUAGAAGAGCUAAAGAAA DB 82 SEQ. ID 0203 GUAGAAGAGCUAAAGAAAA DB 83 SEQ. ID 0204 UAGAAGAGCUAAAGAAAAA DB 84 SEQ. ID 0205 AGAAGAGCUAAAGAAAAAA DB 85 SEQ. ID 0206 GAAGAGCUAAAGAAAAAAU DB 86 SEQ. ID 0207 AAGAGCUAAAGAAAAAAUA DB 87 SEQ. ID 0208 AGAGCUAAAGAAAAAAUAC DB 88 SEQ. ID 0209 GAGCUAAAGAAAAAAUACG DB 89 SEQ. ID 0210 AGCUAAAGAAAAAAUACGG DB 90 SEQ. ID 0211 GCUAAAGAAAAAAUACGGG Luc 1 SEQ. ID 0212 AUCCUCAUAAAGGCCAAGA Luc 2 SEQ. ID 0213 AGAUCCUCAUAAAGGCCAA Luc 3 SEQ. ID 0214 AGAGAUCCUCAUAAAGGCC Luc 4 SEQ. ID 0215 AGAGAGAUCCUCAUAAAGG Luc 5 SEQ. ID 0216 UCAGAGAGAUCCUCAUAAA Luc 6 SEQ. ID 0217 AAUCAGAGAGAUCCUCAUA Luc 7 SEQ. ID 0218 AAAAUCAGAGAGAUCCUCA Luc 8 SEQ. ID 0219 GAAAAAUCAGAGAGAUCCU Luc 9 SEQ. ID 0220 AAGAAAAAUCAGAGAGAUC Luc 10 SEQ. ID 0221 GCAAGAAAAAUCAGAGAGA Luc 11 SEQ. ID 0222 ACGCAAGAAAAAUCAGAGA Luc 12 SEQ. ID 0223 CGACGCAAGAAAAAUCAGA Luc 13 SEQ. ID 0224 CUCGACGCAAGAAAAAUCA Luc 14 SEQ. ID 0225 AACUCGACGCAAGAAAAAU Luc 15 SEQ. ID 0226 AAAACUCGACGCAAGAAAA Luc 16 SEQ. ID 0227 GGAAAACUCGACGCAAGAA Luc 17 SEQ. ID 0228 CCGGAAAACUCGACGCAAG Luc 18 SEQ. ID 0229 UACCGGAAAACUCGACGCA Luc 19 SEQ. ID 0230 CUUACCGGAAAACUCGACG Luc 20 SEQ. ID 0231 GUCUUACCGGAAAACUCGA Luc 21 SEQ. ID 0232 AGGUCUUACCGGAAAACUC Luc 22 SEQ. ID 0233 AAAGGUCUUACCGGAAAAC Luc 23 SEQ. ID 0234 CGAAAGGUCUUACCGGAAA Luc 24 SEQ. ID 0235 ACCGAAAGGUCUUACCGGA Luc 25 SEQ. ID 0236 GUACCGAAAGGUCUUACCG Luc 26 SEQ. ID 0237 AAGUACCGAAAGGUCUUAC Luc 27 SEQ. ID 0238 CGAAGUACCGAAAGGUCUU Luc 28 SEQ. ID 0239 GACGAAGUACCGAAAGGUC Luc 29 SEQ. ID 0240 UGGACGAAGUACCGAAAGG Luc 30 SEQ. ID 0241 UGUGGACGAAGUACCGAAA Luc 31 SEQ. ID 0242 UUUGUGGACGAAGUACCGA Luc 32 SEQ. ID 0243 UGUUUGUGGACGAAGUACC Luc 33 SEQ. ID 0244 UGUGUUUGUGGACGAAGUA Luc 34 SEQ. ID 0245 GUUGUGUUUGUGGACGAAG Luc 35 SEQ. ID 0246 GAGUUGUGUUUGUGGACGA Luc 36 SEQ. ID 0247 AGGAGUUGUGUUUGUGGAC Luc 37 SEQ. ID 0248 GGAGGAGUUGUGUUUGUGG Luc 38 SEQ. ID 0249 GCGGAGGAGUUGUGUUUGU Luc 39 SEQ. ID 0250 GCGCGGAGGAGUUGUGUUU Luc 40 SEQ. ID 0251 UUGCGCGGAGGAGUUGUGU Luc 41 SEQ. ID 0252 AGUUGCGCGGAGGAGUUGU Luc 42 SEQ. ID 0253 AAAGUUGCGCGGAGGAGUU Luc 43 SEQ. ID 0254 AAAAAGUUGCGCGGAGGAG Luc 44 SEQ. ID 0255 CGAAAAAGUUGCGCGGAGG Luc 45 SEQ. ID 0256 CGCGAAAAAGUUGCGCGGA Luc 46 SEQ. ID 0257 ACCGCGAAAAAGUUGCGCG Luc 47 SEQ. ID 0258 CAACCGCGAAAAAGUUGCG Luc 48 SEQ. ID 0259 AACAACCGCGAAAAAGUUG Luc 49 SEQ. ID 0260 GUAACAACCGCGAAAAAGU Luc 50 SEQ. ID 0261 AAGUAACAACCGCGAAAAA Luc 51 SEQ. ID 0262 UCAAGUAACAACCGCGAAA Luc 52 SEQ. ID 0263 AGUCAAGUAACAACCGCGA Luc 53 SEQ. ID 0264 CCAGUCAAGUAACAACCGC Luc 54 SEQ. ID 0265 CGCCAGUCAAGUAACAACC Luc 55 SEQ. ID 0266 GUCGCCAGUCAAGUAACAA Luc 56 SEQ. ID 0267 ACGUCGCCAGUCAAGUAAC Luc 57 SEQ. ID 0268 UUACGUCGCCAGUCAAGUA Luc 58 SEQ. ID 0269 GAUUACGUCGCCAGUCAAG Luc 59 SEQ. ID 0270 UGGAUUACGUCGCCAGUCA Luc 60 SEQ. ID 0271 CGUGGAUUACGUCGCCAGU Luc 61 SEQ. ID 0272 AUCGUGGAUUACGUCGCCA Luc 62 SEQ. ID 0273 AGAUCGUGGAUUACGUCGC Luc 63 SEQ. ID 0274 AGAGAUCGUGGAUUACGUC Luc 64 SEQ. ID 0275 AAAGAGAUCGUGGAUUACG Luc 65 SEQ. ID 0276 AAAAAGAGAUCGUGGAUUA Luc 66 SEQ. ID 0277 GGAAAAAGAGAUCGUGGAU Luc 67 SEQ. ID 0278 ACGGAAAAAGAGAUCGUGG Luc 68 SEQ. ID 0279 UGACGGAAAAAGAGAUCGU Luc 69 SEQ. ID 0280 GAUGACGGAAAAAGAGAUC Luc 70 SEQ. ID 0281 ACGAUGACGGAAAAAGAGA Luc 71 SEQ. ID 0282 AGACGAUGACGGAAAAAGA Luc 72 SEQ. ID 0283 AAAGACGAUGACGGAAAAA Luc 73 SEQ. ID 0284 GGAAAGACGAUGACGGAAA Luc 74 SEQ. ID 0285 ACGGAAAGACGAUGACGGA Luc 75 SEQ. ID 0286 GCACGGAAAGACGAUGACG Luc 76 SEQ. ID 0287 GAGCACGGAAAGACGAUGA Luc 77 SEQ. ID 0288 UGGAGCACGGAAAGACGAU Luc 78 SEQ. ID 0289 UUUGGAGCACGGAAAGACG Luc 79 SEQ. ID 0290 GUUUUGGAGCACGGAAAGA Luc 80 SEQ. ID 0291 UUGUUUUGGAGCACGGAAA Luc 81 SEQ. ID 0292 UGUUGUUUUGGAGCACGGA Luc 82 SEQ. ID 0293 GUUGUUGUUUUGGAGCACG Luc 83 SEQ. ID 0294 CCGUUGUUGUUUUGGAGCA Luc 84 SEQ. ID 0295 CGCCGUUGUUGUUUUGGAG Luc 85 SEQ. ID 0296 GCCGCCGUUGUUGUUUUGG Luc 86 SEQ. ID 0297 CCGCCGCCGUUGUUGUUUU Luc 87 SEQ. ID 0298 UCCCGCCGCCGUUGUUGUU Luc 88 SEQ. ID 0299 CUUCCCGCCGCCGUUGUUG Luc 89 SEQ. ID 0300 AACUUCCCGCCGCCGUUGU Luc 90 SEQ. ID 0301 UGAACUUCCCGCCGCCGUU

Example II Validation of the Algorithm Using DBI, Luciferase, PLK, EGFR, and SEAP

The algorithm (Formula VIII) identified siRNAs for five genes, human DBI, firefly luciferase (fLuc), renilla luciferase (rLuc), human PLK, and human secreted alkaline phosphatase (SEAP). Four individual siRNAs were selected on the basis of their SMARTSCORES™ derived by analysis of their sequence using Formula VIII (all of the siRNAs would be selected with Formula IX as well) and analyzed for their ability to silence their targets' expression. In addition to the scoring, a BLAST search was conducted for each siRNA. To minimize the potential for off-target silencing effects, only those target sequences with more than three mismatches against un-related sequences were selected. Semizarov, et al. (2003)

Specificity of short interfering RNA determined through gene expression signatures, Proc. Natl. Acad. Sci. USA, 100:6347. These duplexes were analyzed individually and in pools of 4 and compared with several siRNAs that were randomly selected. The functionality was measured as a percentage of targeted gene knockdown as compared to controls. All siRNAs were transfected as described by the methods above at 100 nM concentration into HEK293 using Lipofectamine 2000. The level of the targeted gene expression was evaluated by B-DNA as described above and normalized to the non-specific control. FIG. 10 shows that the siRNAs selected by the algorithm disclosed herein were significantly more potent than randomly selected siRNAs. The algorithm increased the chances of identifying an F50 siRNA from 48% to 91%, and an F80 siRNA from 13% to 57%. In addition, pools of SMART siRNA silence the selected target better than randomly selected pools (see FIG. 10F).

Example III Validation of the Algorithm Using Genes Involved in Clathrin-Dependent Endocytosis

Components of clathrin-mediated endocytosis pathway are key to modulating intracellular signaling and play important roles in disease. Chromosomal rearrangements that result in fusion transcripts between the Mixed-Lineage Leukemia gene (MLL) and CALM (clathrin assembly lymphoid myeloid leukemia gene) are believed to play a role in leukemogenesis. Similarly, disruptions in Rab7 and Rab9, as well as HIP1 (Huntingtin-interacting protein), genes that are believed to be involved in endocytosis, are potentially responsible for ailments resulting in lipid storage, and neuronal diseases, respectively. For these reasons, siRNA directed against clathrin and other genes involved in the clathrin-mediated endocytotic pathway are potentially important research and therapeutic tools.

siRNAs directed against genes involved in the clathrin-mediated endocytosis pathways were selected using Formula VIII. The targeted genes were clathrin heavy chain (CHC, accession # NM 004859), clathrin light chain A (CLCa, NM_(—)001833), clathrin light chain B (CLCb, NM_(—)001834), CALM (U45976), β2 subunit of AP-2 (β2, NM_(—)001282), Eps15 (NM_(—)001981), Eps15R(NM_(—)021235), dynamin II (DYNII, NM_(—)004945), Rab5a (BC001267), Rab5b (NM-002868), Rab5c (AF141304), and EEA.1 (XM_(—)018197).

For each gene, four siRNAs duplexes with the highest scores were selected and a BLAST search was conducted for each of them using the Human EST database. In order to minimize the potential for off-target silencing effects, only those sequences with more than three mismatches against un-related sequences were used. All duplexes were synthesized at Dharmacon, Inc. as 21-mers with 3′-UU overhangs using a modified method of 2′-ACE chemistry, Scaringe (2000) Advanced 5′-silyl-2′-orthoester approach to RNA oligonucleotide synthesis, Methods Enzymol. 317:3, and the antisense strand was chemically phosphorylated to insure maximized activity.

HeLa cells were grown in Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal bovine serum, antibiotics and glutamine. siRNA duplexes were resuspended in 1× siRNA Universal buffer (Dharmacon, Inc.) to 20CM prior to transfection. HeLa cells in 12-well plates were transfected twice with 4 μl of 20 μM siRNA duplex in 3 μl Lipofectamine 2000 reagent (Invitrogen, Carlsbad, Calif., USA) at 24-hour intervals. For the transfections in which 2 or 3 siRNA duplexes were included, the amount of each duplex was decreased, so that the total amount was the same as in transfections with single siRNAs. Cells were plated into normal culture medium 12 hours prior to experiments, and protein levels were measured 2 or 4 days after the first transfection.

Equal amounts of lysates were resolved by electrophoresis, blotted, and stained with the antibody specific to targeted protein, as well as antibodies specific to unrelated proteins, PP1 phosphatase and Tsg101 (not shown). The cells were lysed in Triton X-100/glycerol solubilization buffer as described previously. Tebar, Bohlander, & Sorkin (1999) Clathrin Assembly Lymphoid Myeloid Leukemia (CALM) Protein: Localization in Endocytic-coated Pits, Interactions with Clathrin, and the Impact of Overexpression on Clathrin-mediated Traffic, Mol. Biol. Cell, 10:2687. Cell lysates were electrophoresed, transferred to nitrocellulose membranes, and Western blotting was performed with several antibodies followed by detection using enhanced chemiluminescence system (Pierce, Inc). Several x-ray films were analyzed to determine the linear range of the chemiluminescence signals, and the quantifications were performed using densitometry and AlphaImager v5.5 software (Alpha Innotech Corporation). In experiments with Eps15R-targeted siRNAs, cell lysates were subjected to immunoprecipitation with Ab860, and Eps15R was detected in immunoprecipitates by Western blotting as described above.

The antibodies to assess the levels of each protein by Western blot were obtained from the following sources: monoclonal antibody to clathrin heavy chain (TD. 1) was obtained from American Type Culture Collection (Rockville, Md., USA); polyclonal antibody to dynamin II was obtained from Affinity Bioreagents, Inc. (Golden, Colo., USA); monoclonal antibodies to EEA. 1 and Rab5a were purchased from BD Transduction Laboratories (Los Angeles, Calif., USA); the monoclonal antibody to Tsg101 was purchased from Santa Cruz Biotechnology, Inc. (Santa Cruz, Calif., USA); the monoclonal antibody to GFP was from ZYMED Laboratories Inc. (South San Francisco, Calif., USA); the rabbit polyclonal antibodies Ab32 specific to α-adaptins and Ab20 to CALM were described previously (Sorkin et al. (1995) Stoichiometric Interaction of the Epidermal Growth Factor Receptor with the Clathrin-associated Protein Complex AP-2, J. Biol. Chem., 270:619), the polyclonal antibodies to clathrin light chains A and B were kindly provided by Dr. F. Brodsky (UCSF); monoclonal antibodies to PP1 (BD Transduction Laboratories) and α-Actinin (Chemicon) were kindly provided by Dr. M. Dell'Acqua (University of Colorado); Eps15 Ab577 and Eps15R Ab860 were kindly provided by Dr. P. P. Di Fiore (European Cancer Institute).

FIG. 11 demonstrates the in vivo functionality of 48 individual siRNAs, selected using Formula VIII (most of them will meet the criteria incorporated by Formula IX as well) targeting 12 genes. Various cell lines were transfected with siRNA duplexes (Dup1-4) or pools of siRNA duplexes (Pool), and the cells were lysed 3 days after transfection with the exception of CALM (2 days) and β2 (4 days).

Note a β1-adaptin band (part of AP-1 Golgi adaptor complex) that runs slightly slower than β2 adaptin. CALM has two splice variants, 66 and 72 kD. The full-length Eps15R (a doublet of ˜130 kD) and several truncated spliced forms of ˜100 kD and ˜70 kD were detected in Eps15R immunoprecipitates (shown by arrows). The cells were lysed 3 days after transfection. Equal amounts of lysates were resolved by electrophoresis and blotted with the antibody specific to a targeted protein (GFP antibody for YFP fusion proteins) and the antibody specific to unrelated proteins PP1 phosphatase or α-actinin, and TSG1101. The amount of protein in each specific band was normalized to the amount of non-specific proteins in each lane of the gel. Nearly all of them appear to be functional, which establishes that Formula VIII and IX can be used to predict siRNAs' functionality in general in a genome wide manner.

To generate the fusion of yellow fluorescent protein (YFP) with Rab5b or Rab5c (YFP-Rab5b or YFP-Rab5c), a DNA fragment encoding the full-length human Rab5b or Rab5c was obtained by PCR using Pfu polymerase (Stratagene) with a SacI restriction site introduced into the 5′ end and a KpnI site into the 3′ end and cloned into pEYFP-C1 vector (CLONTECH, Palo Alto, Calif., USA). GFP-CALM and YFP-Rab5a were described previously (Tebar, Bohlander, & Sorkin (1999) Clathrin Assembly Lymphoid Myeloid Leukemia (CALM) Protein: Localization in Endocytic-coated Pits, Interactions with Clathrin, and the Impact of Overexpression on Clathrin-mediated Traffic, Mol. Biol. Cell 10:2687).

Example IV Validation of the Algorithm Using Eg5, GADPH, ATE1, MEK2, MEK1, QB, LaminA/C, C-myc, Human Cyclophilin, and Mouse Cyclophilin

A number of genes have been identified as playing potentially important roles in disease etiology. Expression profiles of normal and diseased kidneys has implicated Edg5 in immunoglobulin A neuropathy, a common renal glomerular disease. Myc1, MEK1/2 and other related kinases have been associated with one or more cancers, while lamins have been implicated in muscular dystrophy and other diseases. For these reasons, siRNA directed against the genes encoding these classes of molecules would be important research and therapeutic tools.

FIG. 12 illustrates four siRNAs targeting 10 different genes (Table V for sequence and accession number information) that were selected according to the Formula VIII and assayed as individuals and pools in HEK293 cells. The level of siRNA induced silencing was measured using the B-DNA assay. These studies demonstrated that thirty-six out of the forty individual SMART-selected siRNA tested are functional (90%) and all 10 pools are fully functional.

Example V Validation of the Algorithm Using Bcl2

Bcl-2 is a ˜25 kD, 205-239 amino acid, anti-apoptotic protein that contains considerable homology with other members of the BCL family including BCLX, MCL1, BAX, BAD, and BIK. The protein exists in at least two forms (Bcl2a, which has a hydrophobic tail for membrane anchorage, and Bcl2b, which lacks the hydrophobic tail) and is predominantly localized to the mitochondrial membrane. While Bcl2 expression is widely distributed, particular interest has focused on the expression of this molecule in B and T cells. Bcl2 expression is down-regulated in normal germinal center B cells yet in a high percentage of follicular lymphomas, Bcl2 expression has been observed to be elevated. Cytological studies have identified a common translocation ((14; 18)(q32; q32)) amongst a high percentage (>70%) of these lymphomas. This genetic lesion places the Bcl2 gene in juxtaposition to immunoglobulin heavy chain gene (IgH) encoding sequences and is believed to enforce inappropriate levels of gene expression, and resistance to programmed cell death in the follicle center B cells. In other cases, hypomethylation of the Bcl2 promoter leads to enhanced expression and again, inhibition of apoptosis. In addition to cancer, dysregulated expression of Bcl-2 has been correlated with multiple sclerosis and various neurological diseases.

The correlation between Bcl-2 translocation and cancer makes this gene an attractive target for RNAi. Identification of siRNA directed against the bcl2 transcript (or Bcl2-IgH fusions) would further our understanding Bcl2 gene function and possibly provide a future therapeutic agent to battle diseases that result from altered expression or function of this gene.

In Silico Identification of Functional siRNA

To identify functional and hyperfunctional siRNA against the Bcl2 gene, the sequence for Bcl-2 was downloaded from the NCBI Unigene database and analyzed using the Formula VIII algorithm. As a result of these procedures, both the sequence and SMARTSCORES™, or siRNA rankings of the Bcl2 siRNA were obtained and ranked according to their functionality. Subsequently, these sequences were BLAST'ed (database) to insure that the selected sequences were specific and contained minimal overlap with unrealated genes. The SMARTSCORES™, or siRNA rankings for the top 10 Bcl-2 siRNA are identified in FIG. 13.

In Vivo Testing of Bcl-2 SiRNA

Bcl-2 siRNAs having the top ten SMARTSCORES™, or siRNA rankings were selected and tested in a functional assay to determine silencing efficiency. To accomplish this, each of the ten duplexes were synthesized using 2′-O-ACE chemistry and transfected at 100 nM concentrations into cells. Twenty-four hours later assays were performed on cell extracts to assess the degree of target silencing. Controls used in these experiments included mock transfected cells, and cells that were transfected with a non-specific siRNA duplex.

The results of these experiments are presented below (and in FIG. 14) and show that all ten of the selected siRNA induce 80% or better silencing of the Bcl2 message at 100 nM concentrations. These data verify that the algorithm successfully identified functional Bcl2 siRNA and provide a set of functional agents that can be used in experimental and therapeutic environments. siRNA 1 GGGAGAUAGUGAUGAAGUA SEQ. ID NO. 302 siRNA 2 GAAGUACAUCCAUUAUAAG SEQ. ID NO. 303 siRNA 3 GUACGACAACCGGGAGAUA SEQ. ID NO. 304 siRNA 4 AGAUAGUGAUGAAGUACAU SEQ. ID NO. 305 siRNA 5 UGAAGACUCUGCUCAGUUU SEQ. ID NO. 306 sIRNA 6 GCAUGCGGCCUCUGUUUGA SEQ. ID NO. 307 siRNA 7 UGCGGCCUCUGUUUGAUUU SEQ. ID NO. 308 siRNA 8 GAGAUAGUGAUGAAGUACA SEQ. ID NO. 309 siRNA 9 GGAGAUAGUGAUGAAGUAC SEQ. ID NO. 310 siRNA 10 GAAGACUCUGCUCAGUUUG SEQ. ID NO. 311

Bcl2 siRNA: Sense Strand, 5′→3′

Example VI Sequences Selected by the Algorithm

Sequences of the siRNAs selected using Formulas (Algorithms) VIII and IX with their corresponding ranking, which have been evaluated for the silencing activity in vivo in the present study (Formula VIII and IX, respectively) are shown in Table V. It should be noted that the “t” residues in Table V, and elsewhere, when referring to siRNA, should be replaced by “u” residues. TABLE V SEQ. ID FORMULA FORMULA GENE Name NO. FTLLSEQTENCE VIII IX CLTC NM_004859 0312 GAAAGAATCTGTAGAGAAA 76 94.2 CLTC NM_004859 0313 GCAATGAGCTGTTTGAAGA 65 39.9 CLTC NM_004859 0314 TGACAAAGGTGGATAAATT 57 38.2 CLTC NM_004859 0315 GGAAATGGATCTCTTTGAA 54 49.4 CLTA NM_001833 0316 GGAAAGTAATGGTCCAACA 22 55.5 CLTA NM_001833 0317 AGACAGTTATGCAGCTATT 4 22.9 CLTA NM_001833 0318 CCAATTCTCGGAAGCAAGA 1 17 CLTA NM_001833 0319 GAAAGTAATGGTCCAACAG −1 −13 CLTB NM_001834 0320 GCGCCAGAGTGAACAAGTA 17 57.5 CLTB NM_001834 0321 GAAGGTGGCCCAGCTATGT 15 −8.6 CLTB NM_001834 0322 GGAACCAGCGCCAGAGTGA 13 40.5 CLTB NM_001834 0323 GAGCGAGATTGCAGGCATA 20 61.7 CALM U45976 0324 GTTAGTATCTGATGACTTG 36 −34.6 CALM U45976 0325 GAAATGGAACCACTAAGAA 33 46.1 CALM U45976 0326 GGAAATGGAACCACTAAGA 30 61.2 CALM U45976 0327 CAACTACACTTTCCAATGC 28 6.8 EPS15 NM_001981 0328 CCACCAAGATTTCATGATA 48 25.2 EPS15 NM_001981 0329 GATCGGAACTCCAACAAGA 43 49.3 EPS15 NM_001981 0330 AAACGGAGCTACAGATTAT 39 11.5 EPS15 NM_001981 0331 CCACACAGCATTCTTGTAA 33 −23.6 EPS15R NM_021235 0332 GAAGTTACCTTGAGCAATC 48 33 EPS15R NM_021235 0333 GGACTTGGCCGATCCAGAA 27 33 EPS15R NM_021235 0334 GCACTTGGATCGAGATGAG 20 1.3 EPS15R NM_021235 0335 CAAAGACCAATTCGCGTTA 17 27.7 DNM2 NM_004945 0336 CCGAATCAATCGCATCTTC 6 −29.6 DNM2 NM_004945 0337 GACATGATCCTGCAGTTCA 5 −14 DNM2 NM_004945 0338 GAGCGAATCGTCACCACTT 5 24 DNM2 NM_004945 0339 CCTCCGAGCTGGCGTCTAC −4 −63.6 ARF6 AF93885 0340 TCACATGGTTAACCTCTAA 27 −21.1 ARF6 AF93885 0341 GATGAGGGACGCCATAATC 7 −38.4 ARF6 AF93885 0342 CCTCTAACTACAAATCTTA 4 16.9 ARF6 AF93885 0343 GGAAGGTGCTATCCAAAAT 4 11.5 RAB5A BC001267 0344 GCAAGCAAGTCCTAACATT 40 25.1 RAB5A BC001267 0345 GGAAGAGGAGTAGACCTTA 17 50.1 RAB5A BC001267 0346 AGGAATCAGTGTTGTAGTA 16 11.5 RAB5A BC001267 0347 GAAGAGGAGTAGACCTTAC 12 7 RAB5B NM_002868 0348 GAAAGTCAAGCCTGGTATT 14 18.1 RAB5B NM_002868 0349 AAAGTCAAGCCTGGTATTA 6 −17.8 RAB5B NM_002868 0350 GCTATGAACGTGAATGATC 3 −21.1 RAB5B NM_002868 0351 CAAGCCTGGTATTACGTTT −7 −37.5 RAB5C AF141304 0352 GGAACAAGATCTGTCAATT 38 51.9 RAB5C AF141304 0353 GCAATGAACGTGAACGAAA 29 43.7 RAB5C AF141304 0354 CAATGAACGTGAACGAAAT 18 43.3 RAB5C AF141304 0355 GGACAGGAGCGGTATCACA 6 18.2 EEA1 XM_018197 0356 AGACAGAGCTTGAGAATAA 67 64.1 EEA1 XM_018197 0357 GAGAAGATCTTTATGCAAA 60 48.7 EEA1 XM_018197 0358 GAAGAGAAATCAGCAGATA 58 45.7 EEA1 XM_018197 0359 GCAAGTAACTCAACTAACA 56 72.3 AP2B1 NM_001282 0360 GAGCTAATCTGCCACATTG 49 −12.4 AP2B1 NM_001282 0361 GCAGATGAGTTACTAGAAA 44 48.9 AP2B1 NM_001282 0362 CAACTTAATTGTCCAGAAA 41 28.2 AP2B1 NM_001282 0363 CAACACAGGATTCTGATAA 33 −5.8 PLK NM_005030 0364 AGATTGTGCCTAAGTCTCT −35 −3.4 PLK NM_005030 0365 ATGAAGATCTGGAGGTGAA 0 −4.3 PLK NM_005030 0366 TTTGAGACTTCTTGCCTAA −5 −27.7 PLK NM_005030 0367 AGATCACCCTCCTTAAATA 15 72.3 GAPDH NM_002046 0368 CAACGGATTTGGTCGTATT 27 −2.8 GAPDH NM_002046 0369 GAAATCCCATCACCATCTT 24 3.9 GAPDH NM_002046 0370 GACCTCAACTACATGGTTT 22 −22.9 GAPDH NM_002046 0371 TGGTTTACATGTTCCAATA 9 9.8 c-Myc 0372 GAAGAAATCGATGTTGTTT 31 −11.7 c-Myc 0373 ACACAAACTTGAACAGCTA 22 51.3 c-Myc 0374 GGAAGAAATCGATGTTGTT 18 26 c-Myc 0375 GAAACGACGAGAACAGTTG 18 −8.9 MAP2K1 NM_002755 0376 GCACATGGATGGAGGTTCT 26 16 MAP2K1 NM_002755 0377 GCAGAGAGAGCAGATTTGA 16 0.4 MAP2K1 NM_002755 0378 GAGGTTCTCTGGATCAAGT 14 15.5 MAP2K1 NM_002755 0379 GAGCAGATTTGAAGCAACT 14 18.5 MAP2K2 NM_030662 0380 CAAAGACGATGACTTCGAA 37 26.4 MAP2K2 NM_030662 0381 GATCAGCATTTGCATGGAA 24 −0.7 MAP2K2 NM_030662 0382 TCCAGGAGTTTGTCAATAA 17 −4.5 MAP2K2 NM_030662 0383 GGAAGCTGATCCACCTTGA 16 59.2 KNSL1(EG5) NM_004523 0384 GCAGAAATCTAAGGATATA 53 35.8 KNSL1(EG5) NM_004523 0385 CAACAAGGATGAAGTCTAT 50 18.3 KNSL1(EG5) NM_004523 0386 CAGCAGAAATCTAAGGATA 41 32.7 KNSL1(EG5) NM_004523 0387 CTAGATGGCTTTCTCAGTA 39 3.9 CyclophilinA NM_021130 0388 AGACAAGGTCCCAAAGACA −16 58.1 CyclophilinA NM_021130 0389 GGAATGGCAAGACCAGCAA −6 36 CyclophilinA NM_021130 0390 AGAATTATTCCAGGGTTTA −3 16.1 CyclophilinA NM_021130 0391 GCAGACAAGGTCCCAAAGA 8 8.9 LAMIN A/C NM_170707 0392 AGAAGCAGCTTCAGGATGA 31 38.8 LAMIN A/C NM_170707 0393 GAGCTTGACTTCCAGAAGA 33 22.4 LAMIN A/C NM_170707 0394 CCACCGAAGTTCACCCTAA 21 27.5 LAMIN A/C NM_170707 0395 GAGAAGAGCTCCTCCATCA 55 30.1 CyclophilinB M60857 0396 GAAAGAGCATCTACGGTGA 41 83.9 CyclophilinB M60857 0397 GAAAGGATTTGGCTACAAA 53 59.1 CyclophilinB M60857 0398 ACAGCAAATTCCATCGTGT −20 28.8 CyclophilinB M60857 0399 GGAAAGACTGTTCCAAAAA 2 27 DBI1 NM_020548 0400 CAACACGCCTCATCCTCTA 27 −7.6 DBI2 NM_020548 0401 CATGAAAGCTTACATCAAC 25 −30.8 DBI3 NM_020548 0402 AAGATGCCATGAAAGCTTA 17 22 DBI4 NM_020548 0403 GCACATACCGCCTGAGTCT 15 3.9 rLUC1 0404 GATCAAATCTGAAGAAGGA 57 49.2 rLUC2 0405 GCCAAGAAGTTTCCTAATA 50 13.7 rLUC3 0406 CAGCATATCTTGAACCATT 41 −2.2 rLUC4 0407 GAACAAAGGAAACGGATGA 39 29.2 SeAP1 NM_031313 0408 CGGAAACGGTCCAGGCTAT 6 26.9 SeAP2 NM_031313 0409 GCTTCGAGCAGACATGATA 4 −11.2 SeAP3 NM_031313 0410 CCTACACGGTCCTCCTATA 4 4.9 SeAP4 NM_031313 0411 GCCAAGAACCTCATCATCT 1 −9.9 fLUC1 0412 GATATGGGCTGAATACAAA 54 40.4 fLUC2 0413 GCACTCTGATTGACAAATA 47 54.7 fLUC3 0414 TGAAGTCTCTGATTAAGTA 46 34.5 fLUC4 0415 TCAGAGAGATCCTCATAAA 40 11.4 mCyclo_1 NM_008907 0416 GCAAGAAGATCACCATTTC 52 46.4 mCyclo_2 NM_008907 0417 GAGAGAAATTTGAGGATGA 36 70.7 mCyclo_3 NM_008907 0418 GAAAGGATTTGGCTATAAG 35 −1.5 mCyclo_4 NM_008907 0419 GAAAGAAGGCATGAACATT 27 10.3 BCL2_1 NM_000633 0420 GGGAGATAGTGATGAAGTA 21 72 BCL2_2 NM_000633 0421 GAAGTACATCCATTATAAG 1 3.3 BCL2_3 NM_000633 0422 GTACGACAACCGGGAGATA 1 35.9 BCL2_4 NM_000633 0423 AGATAGTGATGAAGTACAT −12 22.1 BCL2_5 NM_000633 0424 TGAAGACTCTGCTCAGTTT 36 19.1 BCL2_6 NM_000633 0425 GCATGCGGCCTCTGTTTGA 5 −9.7 QB1 NM_003365.1 0426 GCACACAGCUUACUACAUC 52 −4.8 QB2 NM_003365.1 0427 GAAAUGCCCUGGUAUCUCA 49 22.1 QB3 NM_003365.1 0428 GAAGGAACGUGAUGUGAUC 34 22.9 QB4 NM_003365.1 0429 GCACUACUCCUGUGUGUGA 28 20.4 ATE1-1 NM_007041 0430 GAACCCAGCUGGAGAACUU 45 15.5 ATE1-2 NM_007041 0431 GAUAUACAGUGUGAUCUUA 40 12.2 ATE1-3 NM_007041 0432 GUACUACGAUCCUGAUUAU 37 32.9 ATE1-4 NM_007041 0433 GUGCCGACCUUUACAAUUU 35 18.2 EGFR-1 NM_005228 0434 GAAGGAAACTGAATTCAAA 68 79.4 EGFR-1 NM_005228 0435 GGAAATATGTACTACGAAA 49 49.5 EGFR-1 NM_005228 0436 CCACAAAGCAGTGAATTTA 41 7.6 EGFR-1 NM_005228 0437 GTAACAAGCTCACGCAGTT 40 25.9

Many of the genes to which the described siRNA are directed play critical roles in disease etiology. For this reason, the siRNAs listed in the sequence listing may potentially act as therapeutic agents. A number of prophetic examples follow and should be understood in view of the siRNA that are identified in the sequence listing. To isolate these siRNAs, the appropriate message sequence for each gene is analyzed using one of the before mentioned formulas (preferably formula VIII) to identify potential siRNA targets. Subsequently these targets are BLAST'ed to eliminate homology with potential off-targets.

Example VII Evidence for the Benefits of Pooling

Evidence for the benefits of pooling have been demonstrated using the reporter gene, luciferase. Ninety siRNA duplexes were synthesized using Dharmacon proprietary ACE® chemistry against one of the standard reporter genes: firefly luciferase. The duplexes were designed to start two base pairs apart and to cover approximately 180 base pairs of the luciferase gene (see sequences in Table III). Subsequently, the siRNA duplexes were co-transfected with a luciferase expression reporter plasmid into HEK293 cells using standard transfection protocols and luciferase activity was assayed at 24 and 48 hours.

Transfection of individual siRNAs showed standard distribution of inhibitory effect. Some duplexes were active, while others were not. FIG. 15 represents a typical screen of ninety siRNA duplexes (SEQ. ID NO. 0032-0120) positioned two base pairs apart. As the figure suggests, the functionality of the siRNA duplex is determined more by a particular sequence of the oligonucleotide than by the relative oligonucleotide position within a gene or excessively sensitive part of the mRNA, which is important for traditional anti-sense technology.

When two continuous oligonucleotides were pooled together, a significant increase in gene silencing activity was observed (see FIGS. 16A and B). A gradual increase in efficacy and the frequency of pools functionality was observed when the number of siRNAs increased to 3 and 4 (FIGS. 16A, 16B, 17A, and 17B). Further, the relative positioning of the oligonucleotides within a pool did not determine whether a particular pool was functional (see FIGS. 18A and 18B, in which 100% of pools of oligonucleotides distanced by 2, 10 and 20 base pairs were functional).

However, relative positioning may nonetheless have an impact. An increased functionality may exist when the siRNA are positioned continuously head to toe (5′ end of one directly adjacent to the 3′ end of the others).

Additionally, siRNA pools that were tested performed at least as well as the best oligonucleotide in the pool, under the experimental conditions whose results are depicted in FIG. 19. Moreover, when previously identified non-functional and marginally (semi) functional siRNA duplexes were pooled together in groups of five at a time, a significant functional cooperative action was observed (see FIG. 20). In fact, pools of semi-active oligonucleotides were 5 to 25 times more functional than the most potent oligonucleotide in the pool. Therefore, pooling several siRNA duplexes together does not interfere with the functionality of the most potent siRNAs within a pool, and pooling provides an unexpected significant increase in overall functionality

Example VIII Additional Evidence of the Benefits of Pooling

Experiments were performed on the following genes: P-galactosidase, Renilla luciferase, and Secreted alkaline phosphatase, which demonstrates the benefits of pooling. (see FIGS. 21A, 21B and 21C). Individual and pools of siRNA (described in Figure legends 21A-C) were transfected into cells and tested for silencing efficiency. Approximately 50% of individual siRNAs designed to silence the above-specified genes were functional, while 100% of the pools that contain the same siRNA duplexes were functional.

Example IX Highly Functional siRNA

Pools of five siRNAs in which each two siRNAs overlap to 10-90% resulted in 98% functional entities (>80% silencing). Pools of siRNAs distributed throughout the mRNA that were evenly spaced, covering an approximate 20-2000 base pair range, were also functional. When the pools of siRNA were positioned continuously head to tail relative to mRNA sequences and mimicked the natural products of Dicer cleaved long double stranded RNA, 98% of the pools evidenced highly functional activity (>95% silencing).

Example X Human Cyclophilin B

Table III above lists the siRNA sequences for the human cyclophilin B protein. A particularly functional siRNA may be selected by applying these sequences to any of Formula I to VII above.

Alternatively, one could pool 2, 3, 4, 5 or more of these sequences to create a kit for silencing a gene. Preferably, within the kit there would be at least one sequence that has a relatively high predicted functionality when any of Formulas I-VII is applied.

Example XI Sample Pools of siRNAs and Their Application to Human Disease

The genetic basis behind human disease is well documented and siRNA may be used as both research or diagnostic tools and therapeutic agents, either individually or in pools. Genes involved in signal transduction, the immune response, apoptosis, DNA repair, cell cycle control, and a variety of other physiological functions have clinical relevance and therapeutic agents that can modulate expression of these genes may alleviate some or all of the associated symptoms. In some instances, these genes can be described as a member of a family or class of genes and siRNA (randomly, conventionally, or rationally designed) can be directed against one or multiple members of the family to induce a desired result.

To identify rationally designed siRNA to each gene, the sequence was analyzed using Formula VIII or Formula X to identify rationally designed siRNA. To confirm the activity of these sequences, the siRNA are introduced into a cell type of choice (e.g., HeLa cells, HEK293 cells) and the levels of the appropriate message are analyzed using one of several art proven techniques. siRNA having heightened levels of potency can be identified by testing each of the before mentioned duplexes at increasingly limiting concentrations. Similarly, siRNA having increased levels of longevity can be identified by introducing each duplex into cells and testing functionality at 24, 48, 72, 96, 120, 144, 168, and 192 hours after transfection. Agents that induce >95% silencing at sub-nanomolar concentrations and/or induce functional levels of silencing for >96 hours are considered hyperfunctional.

Example XII Validation of Multigene Knockout Using Rab5 and Eps

Two or more genes having similar, overlapping functions often leads to genetic redundancy. Mutations that knockout only one of, e.g., a pair of such genes (also referred to as homologs) results in little or no phenotype due to the fact that the remaining intact gene is capable of fulfilling the role of the disrupted counterpart. To fully understand the function of such genes in cellular physiology, it is often necessary to knockout or knockdown both homologs simultaneously. Unfortunately, concomitant knockdown of two or more genes is frequently difficult to achieve in higher organisms (e.g., mice) thus it is necessary to introduce new technologies dissect gene function. One such approach to knocking down multiple genes simultaneously is by using siRNA. For example, FIG. 11 showed that rationally designed siRNA directed against a number of genes involved in the clathrin-mediated endocytosis pathway resulted in significant levels of protein reduction (e.g., >80%). To determine the effects of gene knockdown on clathrin-related endocytosis, internalization assays were performed using epidermal growth factor and transferrin. Specifically, mouse receptor-grade EGF (Collaborative Research Inc.) and iron-saturated human transferrin (Sigma) were iodinated as described previously (Jiang, X., Huang, F., Marusyk, A. & Sorkin, A. (2003) Mol Biol Cell 14, 858-70). HeLa cells grown in 12-well dishes were incubated with ¹²⁵I-EGF (1 ng/ml) or ¹²⁵I-transferrin (1 μg/ml) in binding medium (DMEM, 0.1% bovine serum albumin) at 37° C., and the ratio of internalized and surface radioactivity was determined during 5-min time course to calculate specific internalization rate constant k_(c) as described previously (Jiang, X et al.). The measurements of the uptakes of radiolabeled transferrin and EGF were performed using short time-course assays to avoid influence of the recycling on the uptake kinetics, and using low ligand concentration to avoid saturation of the clathrin-dependent pathway (for EGF Lund, K. A., Opresko, L. K., Strarbuck, C., Walsh, B. J. & Wiley, H. S. (1990) J. Biol. Chem. 265, 15713-13723).

The effects of knocking down Rab5a, 5b, 5c, Eps, or Eps 15R (individually) are shown in FIG. 22 and demonstrate that disruption of single genes has little or no effect on EGF or Tfn internalization. In contrast, simultaneous knock down of Rab5a, 5b, and 5c, or Eps and Eps 15R, leads to a distinct phenotype (note: total concentration of siRNA in these experiments remained constant with that in experiments in which a single siRNA was introduced, see FIG. 23). These experiments demonstrate the effectiveness of using rationally designed siRNA to knockdown multiple genes and validates the utility of these reagents to override genetic redundancy.

Example XIII Validation of Multigene Targeting Using G6PD, GAPDH, PLK, and UQC

Further demonstration of the ability to knock down expression of multiple genes using rationally designed siRNA was performed using pools of siRNA directed against four separate genes. To achieve this, siRNA were transfected into cells (total siRNA concentration of 100 nM) and assayed twenty-four hours later by B-DNA. Results shown in FIG. 24 show that pools of rationally designed molecules are capable of simultaneously silencing four different genes.

Example XIV Validation of Multigene Knockouts as Demonstrated by Gene Expression Profiling, a Prophetic Example

To further demonstrate the ability to concomitantly knockdown the expression of multiple gene targets, single siRNA or siRNA pools directed against a collection of genes (e.g., 4, 8, 16, or 23 different targets) are simultaneously transfected into cells and cultured for twenty-four hours. Subsequently, mRNA is harvested from treated (and untreated) cells and labeled with one of two fluorescent probes dyes (e.g., a red fluorescent probe for the treated cells, a green fluorescent probe for the control cells.). Equivalent amounts of labeled RNA from each sample is then mixed together and hybridized to sequences that have been linked to a solid support (e.g., a slide, “DNA CHIP”). Following hybridization, the slides are washed and analyzed to assess changes in the levels of target genes induced by siRNA.

Example XV Identifying Hyperfunctional siRNA

Identification of Hyperfunctional Bcl-2 siRNA

The ten rationally designed Bcl2 siRNA (identified in FIGS. 13, 14) were tested to identify hyperpotent reagents. To accomplish this, each of the ten Bcl-2 siRNA were individually transfected into cells at a 300 pM (0.3 nM) concentrations. Twenty-four hours later, transcript levels were assessed by B-DNA assays and compared with relevant controls. As shown in FIG. 25, while the majority of Bcl-2 siRNA failed to induce functional levels of silencing at this concentration, siRNA 1 and 8 induced >80% silencing, and siRNA 6 exhibited greater than 90% silencing at this subnanomolar concentration.

By way of prophetic examples, similar assays could be performed with any of the groups of rationally designed genes described in the Examples. Thus for instance, rationally designed siRNA sequences directed against a gene of interest could be introduced into cells at increasingly limiting concentrations to determine whether any of the duplexes are hyperfunctional.

Example XVI Gene Silencing: Prophetic Example

Below is an example of how one might transfect a cell.

Select a cell line. The selection of a cell line is usually determined by the desired application. The most important feature to RNAi is the level of expression of the gene of interest. It is highly recommended to use cell lines for which siRNA transfection conditions have been specified and validated.

Plate the cells. Approximately 24 hours prior to transfection, plate the cells at the appropriate density so that they will be approximately 70-90% confluent, or approximately 1×10⁵ cells/ml at the time of transfection. Cell densities that are too low may lead to toxicity due to excess exposure and uptake of transfection reagent-siRNA complexes. Cell densities that are too high may lead to low transfection efficiencies and little or no silencing. Incubate the cells overnight. Standard incubation conditions for mammalian cells are 37° C. in 5% CO₂. Other cell types, such as insect cells, require different temperatures and CO₂ concentrations that are readily ascertainable by persons skilled in the art. Use conditions appropriate for the cell type of interest.

siRNA re-suspension. Add 20 μl siRNA universal buffer to each siRNA to generate a final concentration of 50 μM.

siRNA-lipid complex formation. Use RNase-free solutions and tubes. Using the following table, Table XI: TABLE XI 96-WELL 24-WELL MIXTURE 1 (TRANSIT-TKO-PLASMID DILUTION MIXTURE) Opti-MEM 9.3 μl 46.5 μl TransIT-TKO (1 μg/μl) 0.5 μl 2.5 μl MIXTURE 1 FINAL VOLUME 10.0 μl 50.0 μl MIXTURE 2 (SIRNA DILUTION MIXTURE) Opti-MEM 9.0 μl 45.0 μl siRNA (1 μM) 1.0 μl 5.0 μl MIXTURE 2 FINAL VOLUME 10.0 μl 50.0 μl MIXTURE 3 (SIRNA-TRANSFECTION REAGENT MIXTURE) Mixture 1 10 μl 50 μl Mixture 2 10 μl 50 μl MIXTURE 3 FINAL VOLUME 20 μl 100 μl Incubate 20 minutes at room temperature MIXTURE 4 (MEDIA-SIRNA/TRANSFECTION REAGENT MIXTURE) Mixture 3 20 μl 100 μl Complete media 80 μl 400 μl MIXTURE 4 FINAL VOLUME 100 μl 500 μl Incubate 48 hours at 37° C.

Transfection. Create a Mixture 1 by combining the specified amounts of OPTI-MEM serum free media and transfection reagent in a sterile polystyrene tube. Create a Mixture 2 by combining specified amounts of each siRNA with OPTI-MEM media in sterile 1 ml tubes. Create a Mixture 3 by combining specified amounts of Mixture 1 and Mixture 2. Mix gently (do not vortex) and incubate at room temperature for 20 minutes. Create a Mixture 4 by combining specified amounts of Mixture 3 to complete media. Add appropriate volume to each cell culture well. Incubate cells with transfection reagent mixture for 24-72 hours at 37° C. This incubation time is flexible. The ratio of silencing will remain consistent at any point in the time period. Assay for gene silencing using an appropriate detection method such as RT-PCR, Western blot analysis, immunohistochemistry, phenotypic analysis, mass spectrometry, fluorescence, radioactive decay, or any other method that is now known or that comes to be known to persons skilled in the art and that from reading this disclosure would useful with the present invention. The optimal window for observing a knockdown phenotype is related to the mRNA turnover of the gene of interest, although 24-72 hours is standard. Final Volume reflects amount needed in each well for the desired cell culture format. When adjusting volumes for a Stock Mix, an additional 10% should be used to accommodate variability in pipetting, etc. Duplicate or triplicate assays should be carried out when possible.

Example XVII siRNAs That Target Deubiquitination Enzymes

siRNAs that target nucleotide sequences for deubiquitination enzymes with the NCBI accession numbers denoted below and having sequences generated in silico by the algorithms herein, are provided. In various embodiments, the siRNAs are rationally designed. In various embodiments, the siRNAs are functional or hyperfunctional. These siRNA that have been generated by the algorithms of the present invention include: SEQ +HL,26 ID NO Name siRNASense Accession  438 AMSH AGAAGGAAGCAGAGGAAUU NM_006463  439 AMSH CGGUAGAGGUGAAUGAAGA NM_006463  440 AMSH GGGCAUCACCUGAGAAAGA NM_006463  441 AMSH GAAGAAGGAAGCAGAGGAA NM_006463  442 AMSH CAAUAUGAAUGGAGCUUAU NM_006463  443 AMSH GCUCUGGAGUUGAGAUUAU NM_006463  444 AMSH GUGGAAAACUGAUGAGGAA NM_006463  445 AMSH GAAAGACACAGUAAAGAAA NM_006463  446 AMSH ACACAGAGAACGAAGAAGA NM_006463  447 AMSH AGAAAGACACAGUAAAGAA NM_006463  448 AMSH GAAAAGAAAGACACAGUAA NM_006463  449 AMSH GAAAUUAAGUAGCUCAGAA NM_006463  450 AMSH CAACAGAAGCAGCAGCAAU NM_006463  451 AMSH GAACAUGGCCAUCCAGCAA NM_006463  452 AMSH GCUAACACAUCCCGAAGAA NM_006463  453 AMSH GGAGAUUGCAUUUCCCAAA NM_006463  454 AMSH CAACUGUAACUCAGAAAUU NM_006463  455 AMSH UUACAAAUCUGCUGUCAUU NM_006463  456 AMSH CUAGAAAGCUUUGGAAGUU NM_006463  457 AMSH GAGUUGAGAUUAUCCGAAU NM_006463  458 AMSH CAACACAGAGAACGAAGAA NM_006463  459 AMSH-LP GAGUAGAGAUGGAGAGGAU NM_020799  460 AMSH-LP AAUAGAAACCUGUGGAAUA NM_020799  461 AMSH-LP UGGAGAAUGUAGAGGAAUU NM_020799  462 AMSH-LP UGAUAGAGGCAGAAAGGAA NM_020799  463 AMSH-LP UGAAGAAACUGAAGGAGAU NM_020799  464 AMSH-LP GAAGAAGGAAAUUUGGAAA NM_020799  465 AMSH-LP UAAUACAGUGAGAGGAAUA NM_020799  466 AMSH-LP GAAUGUAUUUGCAGAUCAA NM_020799  467 AMSH-LP UGGAAUACUCUGUGGAAAA NM_020799  468 AMSH-LP GGACCAGACUAUUGUGACA NM_020799  469 AMSH-LP UCUAAUACAGUGAGAGGAA NM_020799  470 AMSH-LP ACGUAGAAUACCAAGAAUA NM_020799  471 AMSH-LP CGUAGAAUACCAAGAAUAU NM_020799  472 AMSH-LP AGAGUUAGCCCGAGGUCAA NM_020799  473 AMSH-LP AGAGAUUGAUAGAGGCAGA NM_020799  474 AMSH-LP UGUAUUUGGAAGAAGGAAA NM_020799  475 AMSH-LP CAUGGAGAAUGUAGAGGAA NM_020799  476 AMSH-LP AUGAAGAAACUGAAGGAGA NM_020799  477 AMSH-LP GGAAGAAGGAAAUUUGGAA NM_020799  478 AMSH-LP GGAAUAGAAACCUGUGGAA NM_020799  479 AMSH-LP UCUAAGUGCUGUUCAGAAU NM_020799  480 AMSH-LP GGAGAAUGUAGAGGAAUUA NM_020799  481 AMSH-LP UCACCAAAGCAUAAAGACA NM_020799  482 AMSH-LP GCAUAAAGACACUGGCAUC NM_020799  483 AMSH-LP GUGGAAUACUCUGUGGAAA NM_020799  484 AMSH-LP AAUUGGAGCAUCAGAGAUU NM_020799  485 AMSH-LP GCAGAAAGGAAGCGGAUUG NM_020799  486 AMSH-LP GGUCUGGAGUAGAGAUGGA NM_020799  487 AMSH-LP CUGAAAAGCAGGAUAUUAU NM_020799  488 AMSH-LP CUUCCUAACCAUCGAGAUU NM_020799  489 BAP1 GAGCAAAGGAUAUGCGAUU NM_004656  490 BAP1 CCACAAGUCUCAAGAGUCA NM_004656  491 BAP1 GAGAAGAGGAAGAAGUUCA NM_004656  492 BAP1 GGGUGCAAGUGGAGGAGAU NM_004656  493 BAP1 CGUGAUUGAUGAUGAUAUU NM_004656  494 BAP1 UCUACGACCUUCAGAGCAA NM_004656  495 BAP1 GGGUCAUCAUGGAGCGUAU NM_004656  496 BAP1 GAGGUAGAGAAGAGGAAGA NM_004656  497 BAP1 UCAAAGAGUCCCAGAAGGA NM_004656  498 BAP1 CCAUCAACGUCUUGGCUGA NM_004656  499 BAP1 AGGAUGACGAGGAGGAUGA NM_004656  500 BAP1 AGGAGGUAGAGAAGAGGAA NM_004656  501 BAP1 AGGCUGAGAUUGCAAACUA NM_004656  502 BAP1 UCAAGGAGGAGGUAGAGAA NM_004656  503 BAP1 UGGAUGGGCUGAAGGUCUA NM_004656  504 BAP1 UGUCAGUGCUGCAGCCCAA NM_004656  505 BAP1 CCAACCUAGUGGAGCAGAA NM_004656  506 BAP1 GUAGAGAAGAGGAAGAAGU NM_004656  507 BAP1 AGGAUGACUAUGAGGAUGA NM_004656  508 BAP1 CAGAUGAUGAGGAUGACUA NM_004656  509 BAP1 AGAGAAGGACCCACAACUA NM_004656  510 BAP1 CGGUUCUGCUGAUGGGCAA NM_004656  511 BAP1 AGGAAGAAGUUCAAGAUUG NM_004656  512 BAP1 AGGAAGGCAUGCUGGCCAA NM_004656  513 BAP1 CUGGAUCAAUGAAUGAAUA NM_004656  514 BAP1 AACCCAAGCUAGUGGUGAA NM_004656  515 BAP1 CCAAGGAGCUGCUGGCACU NM_004656  516 BAP1 AGGUAUAAGGGGAAGGGAA NM_004656  517 BAP1 GCAGAGACAGGGUUGCUUA NM_004656  518 BAP1 CCUACAAGGCCAAGCGCCA NM_004656  519 C10ORF29 GAUGAUGACUGGAGGCAAA NM_152586  520 C10ORF29 UAACCUAUCCAGAGAGAAA NM_152586  521 C10ORF29 GAUAGAAGUUUGUCAGGUA NM_152586  522 C10ORF29 GUGAGGAAGCCUUUGGAAA NM_152586  523 C10ORF29 AGUACAGGUUUCAAGGAUA NM_152586  524 C10ORF29 CAGGAAGGACUUUGAACUA NM_152586  525 C10ORF29 GCAGUACAGUGCAGAGAAU NM_152586  526 C10ORF29 GCAGCACAGUCAAUGGUAA NM_152586  527 C10ORF29 CCUCAGAAUUGGAGUCUCU NM_152586  528 C10ORF29 GAGCAGGAGACCUCAGAAU NM_152586  529 C10ORF29 AGACAUAUACCAAGAGAAG NM_152586  530 C10ORF29 CAGGGUGGACUGAGAAGAA NM_152586  531 C10ORF29 CCAAACAGGCUCUGCAGAU NM_152586  532 C10ORF29 UCAGGUAGUCUAAGGAAGA NM_152586  533 C12ORF6 UCACAAAGCAGAAGAAUUA NM_020367  534 C12orf6 CAAGAUAGACUUUGCAGAA NM_020367  535 C12ORF6 AGAUAGACUUUGCAGAAAU NM_020367  536 C12orf6 CAAACAAUGAAGUGGAUGA NM_020367  537 C12orf6 GUGAAUUUGUGGAAGCAAU NM_020367  538 C12ORF6 ACAAUGAAGUGGAUGACAU NM_020367  539 C12ORF6 GAGAUUACAUAAACGGAGA NM_020367  540 C12ORF6 GUUUCUUGCUCGAGUGCUA NM_020367  541 C12ORF6 GAUGAUACCUGGAACCCAA NM_020367  542 C12orf6 CAGAAAUGAAGCAAAUGAA NM_020367  543 C12ORF6 GCAGAAAUGAAGCAAAUGA NM_020367  544 C12ORF6 GGAGCUAUGUGAAUUUAUA NM_020367  545 C12orf6 CAGCAGUGAAUUUGUGGAA NM_020367  546 C12orf6 GGGAGAAUGUGAAUACUCA NM_020367  547 C12ORF6 CAACAAACAAUGAAGUGGA NM_020367  548 C12orf6 GAAGCAAUCUGCAUUCAUA NM_020367  549 C12ORF6 GCACAAUCAAACACAUGAA NM_020367  550 C12ORF6 UCUGCAAAGAUGACAUAAA NM_020367  551 C12ORF6 UGACAUAAAGCAUGGGAAC NM_020367  552 C12ORF6 CAAAGAUGACAUAAAGCAU NM_020367  553 C12orf6 GCAAAGAUGACAUAAAGCA NM_020367  554 C12ORF6 GAACCUAUUUUGCUAGAGA NM_020367  555 C12ORF6 GCCUCAGAUUAAUGAACAA NM_020367  556 C12orf6 AAGAUAGACUUUGCAGAAA NM_020367  557 C12orf6 CAAGGAAGCUUUAUUCUUU NM_020367  558 C12ORF6 GACAUGGACACGUCAGAUA NM_020367  559 C12ORF6 CCUGAGUACUUGAUAGACU NM_020367  560 C12ORF6 CUUCCAAAGACGGGAGCUA NM_020367  561 C12ORF6 GGAGUUCUUUUGCAGGAAA NM_020367  562 C12ORF6 UUGCUAAUCUCUUUGGGAA NM_020367  563 C14orf137 CAGACUGGCUGGAGAAAUU NM_023112  564 C14orf137 GGGAAAACAUAGUGGAUGA NM_023112  565 C14orf137 UGAGAUUCCUUGUGUGAAA NM_023112  566 C14orf137 GAACAAUUAGCAACAGAAA NM_023112  567 C14orf137 ACAAUUAGCAACAGAAAGA NM_023112  568 C14orf137 GAGGAAAAGCUCAAGGUUA NM_023112  569 C14orf137 GCCGAUAAACAUUGAUUAA NM_023112  570 C14orf137 CCACCAUGGUCUAUGAGAA NM_023112  571 C14orf137 AAACAUUCUCCUAGCAUUA NM_023112  572 C14orf137 CAACAAUACCUAUGUGUCA NM_023112  573 C14orf137 CCACCUGGACAGAGGCUUA NM_023112  574 C140RF137 AGGAUUUACCGGAGGAAAA NM_023112  575 C140RF137 UGGUGGAACUGGUAGAGAA NM_023112  576 C14orf137 UCACUGGAUUAUUGGUUAA NM_023112  577 C140RF137 GGGAGAUCUUCAAGUUCAA NM_023112  578 C140RF137 GGAGGAAAAUCGAGGAACU NM_023112  579 C14orf137 GGGAACAAUUAGCAACAGA NM_023112  580 C14orf137 CCAAUAGCACUCUCAGAUA NM_023112  581 C14orf137 UCUGGAUACUUCAAGGAUA NM_023112  582 C14or1137 CCGUUUACCUGCUCUAUAA NM_023112  583 C140RF137 UCUACAGGGCCUUGGGCUA NM_023112  584 C140RF137 UGGAACUGGUAGAGAAGGA NM_023112  585 C14orf137 GGACAAAUGCUUUCUAACU NM_023112  586 C14orf137 GGACAGAGGCUUACAAGAC NM_023112  587 C14orf137 GGCCAUACCCCUUAAAUAA NM_023112  588 C14orf137 CCUCAGGACCUUCAAGAUU NM_023112  589 C14orf137 CUGCAGGGAUUUACUGGAA NM_023112  590 C14orf137 GGAACAAUUAGCAACAGAA NM_023112  591 C14orf137 GGUUCUAACUUCAGCAUUC NM_023112  592 C14orf137 CAAUAGCACUCUCAGAUAU NM_023112  593 C15ORF16 GGAAAGACGACAACGAUAA NM_130901  594 C15ORF16 GGGAAAGACGACAACGAUA NM_130901  595 C15ORF16 AGGACAAGGAGAAGGAGAA NM_130901  596 C15ORF16 GCAAGGAGAAGAAGGCCAA NM_130901  597 C15ORF16 GGACCUGGUGUUACGGAAA NM_130901  598 C15ORF16 AGGCAACAAUGGUGGCUUU NM_130901  599 C15ORF16 GCGUGUACAGCGAGGAUUU NM_130901  600 C15ORF16 AGAAGGAGAAGCAGCGCAA NM_130901  601 C15ORF16 CCACGCAGCUGGUGCUCAA NM_130901  602 C15ORF16 CCAAGCAGCCAGAGCGAGA NM_130901  603 C15ORF16 GAACAGAGAGACCAGCAAA NM_130901  604 C15ORF16 AGACCAGCAAAGAGAACAA NM_130901  605 C15ORF16 CCACGUACCCGCAGCAGAA NM_130901  606 C15ORF16 ACGGCAAGGACAAGGAGAA NM_130901  607 C15ORF16 GAGACCUGCUGGAAGGCAA NM_130901  608 C15ORF16 GUUAAGAGACUCAGGUGGA NM_130901  609 C15ORF16 ACGAGGAGAUGAUCGGCUA NM_130901  610 C15ORF16 GGCAAGAACGGCAAGGACA NM_130901  611 C15ORF16 UGACGGAUUCUGAGCACAA NM_130901  612 C15ORF16 CGCUAGAAGCCAAGCUGAA NM_130901  613 C15ORF16 GGUUCUGGCCUAUGAUCAA NM_130901  614 C15ORF16 GAGAAGCAGCGCAAGGAGA NM_130901  615 C6.1A GAAUAAAUCAGGAGACAAA NM_024332  616 C6.1A CCACAAAACUCAACAAUAA NM_024332  617 C6.1A GGGAAAGAGUUUAUGAAUU NM_024332  618 C6.1A AGGAAAGGUAUGAGAGAAU NM_024332  619 C6.1A CAACAGAGGCAGAGAGGUU NM_024332  620 C6.1A GGAACUAACUGUUGAUACA NM_024332  621 C6.1A GAGAGAACCCAGAAAUAAA NM_024332  622 C6.1A GAAUAAAGUCUGUAGUCUA NM_024332  623 C6.1A AGGAAGAGCUUAUGCAAGA NM_024332  624 C6.1A GCACAGAGAAGGAGGAAGU NM_024332  625 C6.1A GCAAUUCAAUGGAGGAAGA NM_024332  626 C6.1A GAGGAAGGACCGAGUAGAA NM_024332  627 C6.1A GGACCUACAUACACACAAA NM_024332  628 C6.1A CGUCAGAAUUGUUCACAUU NM_024332  629 C6.1A AAGAUAAGCUACAGAUUGA NM_024332  630 C6.1A AGAAGGAAGAGGAAAGGUA NM_024332  631 C6.1A GAAGAUAAGAACACAAAGA NM_024332  632 C6.1A GCAUAUACUGGAACUGAAA NM_024332  633 C6.1A CAGAGAAGGAGGAAGUAAU NM_024332  634 C6.1A AGGACAGACUGGAGCAAAA NM_024332  635 C6.1A GCAGAGGAACAGACACAUA NM_024332  636 C6.1A GAAUAGCCUUUCUGACAAA NM_024332  637 C6.1A GAACAGACACAUACGUCAA NM_024332  638 C6.1A GAGGAAAGGUAUGAGAGAA NM_024332  639 C6.1A AGGUAUGAGAGAAUCGAAA NM_024332  640 C6.1A GACAUUCAUUCCAGAGAAA NM_024332  641 C6.1A GGAAGGACCGAGUAGAAAU NM_024332  642 C6.1A GUACAGCCACUCUGGGAAA NM_024332  643 C6.1A GGGCCAGAAGGAAGAGGAA NM_024332  644 C6.1A UAGAAUAAAUCAGGAGACA NM_024332  645 CEZANNE CAAAGAUGAUAGUGACAAU NM_020205  646 CEZANNE GCACUGAGACACUGGAGAA NM_020205  647 CEZANNE UGGCAGAACAGAAGCAGAA NM_020205  648 CEZANNE CAGCUGAGUCUGUUGGUAA NM_020205  649 CEZANNE CUGAGACACUGGAGAAGAA NM_020205  650 CEZANNE GGGCAAGGAGGCUAAACAA NM_020205  651 CEZANNE GCAGAGAGGAAGAUCAUGA NM_020205  652 CEZANNE GGAAAGAAUUGGGAUGUGA NM_020205  653 CEZANNE AGAAGGGAGUUGAGAAGGA NM_020205  654 CEZANNE CAAAGGAGGUUCUCAGUCA NM_020205  655 CEZANNE CCGAUUGGCCAGUGUAAUU NM_020205  656 CGI-77 CAUUAUAGUUGGUGAAGAA NM_016023  657 CGI-77 CAGAAGAAUUUCAGAAGUA NM_016023  658 CGI-77 ACAGAAACAUAGAGAGGAA NM_016023  659 CGI-77 GAGAGGAACUGGAGCAAUU NM_016023  660 CGI-77 ACAUAUGGAAAGUGAGAAA NM_016023  661 CGI-77 GCACAAAAGAGACGGGAAA NM_016023  662 CGI-77 ACAAACACCAAUAGAGAUA NM_016023  663 CGI-77 GUAUAAAGCCAUUGAAGAU NM_016023  664 CGI-77 GCAAAGAGAAGAAGGAGUU NM_016023  665 CGI-77 GGAAAAGGAGCGAGAAGAA NM_016023  666 CGI-77 CGAAGAGCUUGAUGAGGAA NM_016023  667 CGI-77 GCAGCUAGACAGUUAGAAA NM_016023  668 CGI-77 GAAGAUCAACUGAAAGAAA NM_016023  669 CG1-77 CCGAAGAGCUUGAUGAGGA NM_016023  670 CGI-77 AAGAAAUGGAACAGAAACA NM_016023  671 CGI-77 AAAGAAAGCUGCAUUGGAA NM_016023  672 CGI-77 CAGAAGUACUGUGAAGAUA NM_016023  673 CGI-77 GAAAUGGAACAGAAACAUA NM_016023  674 CGI-77 GGAGCGAGAAGAACGGAUA NM_016023  675 CGI-77 GAGACAUGCAUAUGGCUUA NM_016023  676 CGI-77 AGACAUAUGGAAAGUGAGA NM_016023  677 CGI-77 GCUCAAAUAUUGGCAGCUA NM_016023  678 CGI-77 GGUAUUGACCGAAGAGCUU NM_016023  679 CGI-77 AGAAGGAGUUGCAAGCCAA NM_016023  680 CGI-77 ACUUGGUGCUUGAGAAUCA NM_016023  681 CGI-77 CAAUUGAAGCUGACUACUA NM_016023  682 CGI-77 CCAGACAUAUGGAAAGUGA NM_016023  683 CGI-77 GCUGAGAAGGCAUCGCAAA NM_016023  684 CGI-77 UGACUACUAAGGAGAAUAA NM_016023  685 CGI-77 CUAAGGAGAAUAAGAUAGA NM_016023  686 COPS5 GGACAUACCCAAAGGGCUA NM_006837  687 COPS5 CUACAAACCUCCUGAUGAA NM_006837  688 COPS5 UGGAAUAAAUACUGGGUGA NM_006837  689 COPS5 UGAAAGACAGUAUGAGAAA NM_006837  690 COPS5 GGACUAAGGAUCACCAUUA NM_006837  691 COPS5 ACAAAUACGACAAGAAACA NM_006837  692 COPS5 GGUGAAACCAUGAUCAUUA NM_006837  693 COPS5 CCGAAAAUCAGAAGACAAA NM_006837  694 COPS5 GGAUUGAUGUCUCAGGUUA NM_006837  695 COPS5 AACAAUAUCCGCAGGGAAA NM_006837  696 COPS5 CUACAAAUACGACAAGAAA NM_006837  697 COPS5 GUGAAUACGUUGAGUUCUU NM_006837  698 COPS5 UAGGAAAGGUGGAUGGUGA NM_006837  699 COPS5 GAACAAUAUCCGCAGGGAA NM_006837  700 COPS5 AUACAUGGCUGCAUACAUA NM_006837  701 COPS5 ACAAGAAACAGCAGCAAGA NM_006837  702 COPS5 CUGAAAGACAGUAUGAGAA NM_006837  703 COPS5 GAGAAGUACUUUACCUGAA NM_006837  704 COPS5 AAGAAACAGCAGCAAGAAA NM_006837  705 COPS5 AGAAACAGCAGCAAGAAAU NM_006837  706 COPS5 CUUGAGCUGUUGUGGAAUA NM_006837  707 COPS5 GGAGUUUCAUGUUGGGUUU NM_006837  708 COPS5 CGGCGAAGCCCUGGACUAA NM_006837  709 COPS5 CCUUAGAAGUCUCAUAUUU NM_006837  710 COPS5 UAGAAACGCAUGACCGAAA NM_006837  711 COPS5 CCUGAAAGACAGUAUGAGA NM_006837  712 COPS5 GAAUAAAUACUGGGUGAAU NM_006837  713 COPS5 AUGAAUACAUGGCUGCAUA NM_006837  714 COPS5 GGAAUAAAUACUGGGUGAA NM_006837  715 COPS5 GGUGAUUGAUCCAACAAGA NM_006837  716 CYLD UGAAAGAAUUGGAGUGAUA NM_015247  717 CYLD GGAAGAAGGUCGUGGUCAA NM_015247  718 CYLD GGGUAGAACCUUUGCUAAA NM_015247  719 CYLD CUUCAAGAAUGCAGCGUUA NM_015247  720 CYLD CCGAAGAGGCUGAAUCAUA NM_015247  721 CYLD CAUAAUAAACCAAAGGCUA NM_015247  722 CYLD GCUCAUUGGCUGAAGUUAA NM_015247  723 CYLD AAAGGAUGUUGUAGAGAUA NM_015247  724 CYLD AUGUAUGAGUGUAGAGAAU NM_015247  725 CYLD CCGGAUAUGUGGAGGGCUU NM_015247  726 CYLD CUGUAAUGGAAGAGCUAAA NM_015247  727 CYLD GUGAAGUAGUAGAAGAAAA NM_015247  728 CYLD CGAAGAGGCUGAAUCAUAA NM_015247  729 CYLD UGGCUGAAGUUAAGGAGAA NM_015247  730 CYLD AAGUAAAGGCCUCCAAAUA NM_015247  731 CYLD AGGAUGUUGUAGAGAUAAA NM_015247  732 CYLD UGGGAGAGAUGGAUAUUUA NM_015247  733 CYLD CAGAAACAGACUAAGUAAA NM_015247  734 CYLD GAAAAGAAAGCUUAGGAUA NM_015247  735 CYLD GAGUUGAAUUGCUGGAAGA NM_015247  736 CYLD GGAUUUACCUCUGAAGAAA NM_015247  737 CYLD GGGAAGUAUAGGACAGUAU NM_015247  738 CYLD CACAAUGAGUUCAGGCUUA NM_015247  739 CYLD AGAGAUAUCUACAGACUUU NM_015247  740 CYLD UAGUGAAACCCAAGAGCUA NM_015247  741 CYLD AAGAAGGCUUGGAGAUAAU NM_015247  742 CYLD CAGAGUUACUUUUGGCAAU NM_015247  743 CYLD AAGUGAAGUAGUAGAAGAA NM_015247  744 CYLD AGAAAAUACUCCACCAAAA NM_015247  745 CYLD AGAUAAUGAUUGGGAAGAA NM_015247  746 DKFZP434D0127 GAAGGAUACUAAUGGGUAA NM_032147  747 DKFZP434D0127 CCAACGAGUUACUGAGAAU NM_032147  748 DKFZP434D0127 GGGACUGACCUCUGAGUUA NM_032147  749 DKFZP434D0127 UCACAGAAGCCCAGAAACA NM_032147  750 DKFZP434D0127 AAACGAAGGCCAAUAGUAA NM_032147  751 DKFZP434D0127 GUAGAAAGAUGGAACUUAU NM_032147  752 DKFZP434D0127 UGAAAGAGGUUGAUUUGUA NM_032147  753 DKFZP434D0127 GAAAGAGGUUGAUUUGUAA NM_032147  754 DKFZP434D0127 GGAAUUUCUUUGUGAACUU NM_032147  755 DKFZP434D0127 CCAGAAACAACUUAUGAUA NM_032147  756 DKFZP434D0127 GCAUUUGCCCUGAUGGAAA NM_032147  757 DKFZP434D0127 AAUAGUAACUCCUGGUGUA NM_032147  758 DKFZP434D0127 GUAAUAACCGAGAGAAGAU NM_032147  759 DKFZP761A052 CAACACAUUCCAUGGGAUA NM_017602  760 DKFZP761A052 UGUUUUAGCUCUUGCCAAA NM_017602  761 DKFZP761A052 UGCAUGAGGUUGUGCGAAA NM_017602  762 DKFZP761A052 UGGACUAUCUGAUGAAGAA NM_017602  763 DKFZP761A052 CCACCUACAUUAACAGGAA NM_017602  764 DKFZP761A052 CGGAAUAUCCACUAUAAUU NM_017602  765 DKFZP761A052 UGAUGAAGAAUGCCAUAAA NM_017602  766 DKFZP761A052 CAACAGUGAGGACGAGUAU NM_017602  767 DKFZP761A052 CAGCACGCAUCGAGGCUAU NM_017602  768 DKFZP761A052 GAGCAGUCUCUGAUGAAGA NM_017602  769 DKFZP761A052 GCUACAACAGUGAGGACGA NM_017602  770 DKFZP761A052 ACAGUGAGGACGAGUAUGA NM_017602  771 DKFZP761A052 CAACAGGAAUACCUAGACA NM_017602  772 DKFZP761A052 CAGCAAGCGGCGACGUCAA NM_017602  773 DKFZP761A052 CAGGAGCAUUGGUUUGAAA NM_017602  774 DKFZP761A052 AAAACAAAGUGCACAGAGA NM_017602  775 DKFZP761A052 CUGUGGAGGUGUACCAGUA NM_017602  776 DKFZP761A052 GCAUGGACUAUCUGAUGAA NM_017602  777 DKFZP761A052 CUGCAGUGGUUGCGGGAUC NM_017602  778 DKFZP761A052 GAUGCUAGAAGACAAGAAA NM_017602  779 DKFZP761A052 ACAUUAACAGGAAGCGGAA NM_017602  780 DKFZP761A052 CUAGACAGUAUGAAGAAAA NM_017602  781 DKFZP761A052 CCGACUACUUCUCCAACUA NM_017602  782 DKFZP761A052 CCUAGACAGUAUGAAGAAA NM_017602  783 DKFZP761A052 AUUAACAGGAAGCGGAAAA NM_017602  784 DKFZP761A052 GUUAGCUACCAUCGGAAUA NM_017602  785 DKFZP761A052 CUGACCAGGUGUAUGGAGA NM_017602  786 DKFZP761A052 AGUCAUGGAUUGAACAGCA NM_017602  787 DKFZP761A052 UGAUGAAGAAUGCCGACUA NM_017602  788 DKFZP761A052 GCAACCACAUUGAGAUGCA NM_017602  789 E2-EPF CCUCCAACUCUGUCUCUAA NM_014501  790 E2-EPF GGCACUGGGACCUGGAUUU NM_014501  791 E2-EPF ACAAGGAGGUGACGACACU NM_014501  792 E2-EPF GGAGAACUACGAGGAGUAU NM_014501  793 E2-EPF UCAAGUGCCUGCUGAUCCA NM_014501  794 E2-EPF GACACGUACUGCUGACCAU NM_014501  795 E2-EPF CCGCAGCCAUGAACUCCAA NM_014501  796 E2-EPF GCUACUUCCUGACCAAGAU NM_014501  797 E2-EPF GGAGGUCUGUUCCGCAUGA NM_014501  798 E2-EPF ACUGGGACCUGGAUUUGUU NM_014501  799 E2-EPF UCAAGGUCUUUCCCAACGA NM_014501  800 E2-EPF GCACUGGGACCUGGAUUUG NM_014501  801 E2-EPF GUACUGCUGACCAUCAAGU NM_014501  802 FBXO7 GGAAAGAACUGUACAGGAA NM_012179  803 FBXO7 GUGCUGAUCUCGAGUGUUA NM_012179  804 FBXO7 CCAGAAACCUUUUAAGAGA NM_012179  805 FBXO7 GAAUAUGACCAAAGACCAA NM_012179  806 FBXO7 AGGAAGAGGCACAUACAAA NM_012179  807 FBXO7 UGAGAUUAGAAGUGUGAAA NM_012179  808 FBXO7 ACAAAGAUCUUCAGAAACU NM_012179  809 FBXO7 CCGGAGAAGUGGAAGUUGA NM_012179  810 FBXO7 GCGUGAUUUUCGAGACAAU NM_012179  811 FBXO7 CCUGUGUGCCUUUGGGAAA NM_012179  812 FBXO7 ACUCCAGAAUAAUGAGCAA NM_012179  813 FBXO7 GCACAUACAAAGAAAAGAA NM_012179  814 FBXO7 CCUUGAUAGUGUUGAUACA NM_012179  815 FBXO7 CAUUAGAGACCUUGUAUCA NM_012179  816 FBXO7 CCGAAAGGGCGGUUUGUGA NM_012179  817 FBXO7 AGACUAGCAUACAGGAUGA NM_012179  818 FBXO7 UAGCAUACAGGAUGAACAA NM_012179  819 FBXO7 GAAACCUGAUUGUUGUAAA NM_012179  820 FBXO7 CAAAGAGAAACUAGGGGAA NM_012179  821 FBXO7 GAACCUACCAGAUGUAUUU NM_012179  822 FBXO7 AAAGAACUGUACAGGAAGA NM_012179  823 FBXO7 CUGAGUCAAUUCAAGAUAA NM_012179  824 FBXO7 CUGUACAGGAAGAGGCACA NM_012179  825 FBXO7 GUGAAUCGGUGGAAGGGCA NM_012179  826 FBXO7 CCACAGAUUCAGAGCAUUC NM_012179  827 FBXO7 GAAUGACGACAGUAUGUUA NM_012179  828 FBXO7 GAUGAACAACCAAGUGAUU NM_012179  829 FBXO7 AGACACAGAUUGGAAAGAA NM_012179  830 FBXO7 AGAGGCACAUACAAAGAAA NM_012179  831 FBXO7 GGGUGUAUAAGCUGCAGUA NM_012179  832 FBXO8 CGAAAGAACAGGAAGGAUU NM_012180  833 FBXO8 CCAAAUGCACUGAGAGAAU NM_012180  834 FBXO8 UGGCAAGGGUUGUGCAAAU NM_012180  835 FBXO8 GGAGAAUGGCUGCGAGCAA NM_012180  836 FBXO8 GGAGAGAUGUCUUGGAUGA NM_012180  837 FBXO8 CCAAGGAGGCAUUGACAUA NM_012180  838 FBXO8 UGAAGAGCGUGGAGAGUAU NM_012180  839 FBXO8 GAAAUCAGUUCUUGCCAAA NM_012180  840 FBXO8 CAGAUGAGGGAGUGAACUA NM_012180  841 FBXO8 GCAAGGAAAUCGAAAGAAC NM_012180  842 FBXO8 GAACCCACCUUUAGGAUUU NM_012180  843 FBXO8 CGCCAAAGGAAAUAGCAAA NM_012180  844 FBXO8 GAUGAUUCGCCAAAGGAAA NM_012180  845 FBXO8 GCUGUUAACGAAUGAUAAA NM_012180  846 FBXO8 AAGCAGAGCCACUGUCUAA NM_012180  847 FBXO8 GCAUUAGAUUUGCCUGAAA NM_012180  848 FBXO8 GAAGAGUGUUGAUUUGUUA NM_012180  849 FBXO8 GAGAAUCUAUCUUGAUGAA NM_012180  850 FBXO8 UGUGGAGAGUGGUCAGAAA NM_012180  851 FBXO8 GGUCAAGGGUUGUGGAGAG NM_012180  852 FBXO8 GGACAAGUAAAGUUUGAAU NM_012180  853 FBXO8 AGGCAAGGAAAUCGAAAGA NM_012180  854 FBXO8 CACCAAUCAUCGUAAACAA NM_012180  855 FBXO8 CAAUAAGAACCCACCUUUA NM_012180  856 FBXO8 GCCCUCAUGUGAAGAAUAA NM_012180  857 FBXO8 GGUAAGUCCUUUAAACCAU NM_012180  858 FBXO8 UGAUUUAAUGCGAGAACUU NM_012180  859 FBXO8 CCAAGGACUUAGCAGAUAU NM_012180  860 FBXO8 CAGGAAGGAUUCAUUAAUU NM_012180  861 FBXO8 GAACAGGAAGGAUUCAUUA NM_012180  862 FBXW3 GGGAAGAGUACAAGGACAA NM_012165  863 FBXW3 GGGCAAGGCGGAAGAGGAA NM_012165  864 FBXW3 GGAUGCAGCUAGAGGAUGA NM_012165  865 FBXW3 GAAAGAGGCACAAGGAAGA NM_012165  866 FBXW3 CAUCCAGACUGAAGACCAA NM_012165  867 FBXW3 GGCACAAGGAAGAAAGUAU NM_012165  868 FBXW3 GGGAAAGAGGCACAAGGAA NM_012165  869 FBXW3 UGACACACUUGGACAGAGA NM_012165  870 FBXW3 GGACAAGGAGGUCAGGUUU NM_012165  871 FBXW3 GGAAGAUUGGCCUUGGUAA NM_012165  872 FBXW3 GGAUGAUGCUUUGUACAUA NM_012165  873 FBXW3 GAAGGAAGGGGAAGAGGAA NM_012165  874 FBXW3 ACACUUGGACAGAGACUUU NM_012165  875 FBXW3 CAGUGAAGGUGUCUCAGAA NM_012165  876 FBXW3 GAUGAUGCUUUGUACAUAU NM_012165  877 FBXW3 GAAGAAAGUAUGGGAAGGA NM_012165  878 FBXW3 CCGCACCAGUGUCCGGAAA NM_012165  879 FBXW3 AGGAGGAGAUGGGAAGAUU NM_012165  880 FBXW3 UGAACUGUGUGGAUUGCAA NM_012165  881 FBXW3 GAAGAUUGGCCUUGGUAAG NM_012165  882 FBXW3 AAGUGGAGAUGCAGUCAGA NM_012165  883 FBXW3 GAACUGUGUGGAUUGCAAA NM_012165  884 FBXW3 GCACAAGGAAGAAAGUAUG NM_012165  885 FBXW3 GGAGGUGAACUGUGUGGAU NM_012165  886 FBXW3 GUACAUAUCCCAGGCUAAU NM_012165  887 FBXW3 CGGGAAAGAGGCACAAGGA NM_012165  888 FBXW3 GAGGUGAACUGUGUGGAUU NM_012165  889 FBXW3 GGCGAGAGGCAUCAUCAAA NM_012165  890 FBXW3 CCAGAUGGUGCCAGCUUGA NM_012165  891 FBXW3 GAUUGGCCUUGGUAAGAUU NM_012165  892 FLJ11807 AGACCAAGAUCCAGAAAGA NM_024954  893 FLJ11807 CGGGAUGAGUUCUGGGACA NM_024954  894 FLJ11807 CUGAAGAAAGAGCGGCUUA NM_024954  895 FLJ11807 GCAAUGAGCCCCUGAAGAA NM_024954  896 FLJ11807 GCUACGAUGAGCUGGGCAA NM_024954  897 FLJ11807 GAGCAAACGGGAUGAGUUC NM_024954  898 FLJ11807 CCAGAAAGAUUUUGUCAUC NM_024954  899 FLJ11807 ACCAAGAUCCAGAAAGAUU NM_024954  900 FLJ11807 CCAAGAUCCAGAAAGAUUU NM_024954  901 FLJ11807 CUUGCAACCUUGUCAGAGA NM_024954  902 FLJ11807 CUUAAGUGGAAGAGCGACU NM_024954  903 FLJ11807 GGAGCAAACGGGAUGAGUU NM_024954  904 FLJ11807 CAGCACAAUUGGCAGAGAU NM_024954  905 FLJ11807 CCGGGAAGCUGCUCACAGA NM_024954  906 FLJ11807 CAAGCGAGCAGGACGCAAU NM_024954  907 FLJ11807 UGAAGAAAGAGCGGCUUAA NM_024954  908 FLJ11807 ACACGGAGGAGGAGAGCCU NM_024954  909 FLJ11807 AAGAGCGGCUUAAGUGGAA NM_024954  910 FLJ11807 GCUACCAGCUGCCCAUCUA NM_024954  911 FLJ11807 UCAUCCAGGUCAUCAUCAA NM_024954  912 FLJ11807 GGAGACCAAGAUCCAGAAA NM_024954  913 FLJ11807 AAGAAAGAGCGGCUUAAGU NM_024954  914 FLJ11807 GCACAAUUGGCAGAGAUGA NM_024954  915 FLJ11807 UUGCAACCUUGUCAGAGAA NM_024954  916 FLJ11807 GCCGUGAGUUCCCGCUGAA NM_024954  917 FLJ11807 CAUGGCACCCUCUGUGAAU NM_024954  918 FLJ11807 GCAAACGGGAUGAGUUCUG NM_024954  919 FLJ11807 CCACACACGGGCCUUGCAA NM_024954  920 FLJ11807 AGAAAGAGCGGCUUAAGUG NM_024954  921 FLJ11807 ACACGGGCCUUGCAACCUU NM_024954  922 FLJ12552 GGUGAUUGAUGUAGGGAAA NM_022832  923 FLJ12552 GGGAGAAUGUGUUGGCAUA NM_022832  924 FLJ12552 AGUCAUAAGUUCAGGAUAU NM_022832  925 FLJ12552 GGGAAAUGUUUGUACUAUA NM_022832  926 FLJ12552 GGAACUGAUUCAUAAGAAA NM_022832  927 FLJ12552 CAGAAGAAUUGGGUAGAUA NM_022832  928 FLJ12552 GCAGGAUGCUCAUGAAUUU NM_022832  929 FLJ12552 GGGUGCAAGUAUAGCUUUA NM_022832  930 FLJ12552 CCAUGAAACUUACGCAGUA NM_022832  931 FLJ12552 UGAGUAACCUCGAUAUUAA NM_022832  932 FLJ12552 UUGGAAGGCUGUAGAAGUA NM_022832  933 FLJ12552 CAGCAUUCAUGGAUAGAUU NM_022832  934 FLJ12552 GCCCAAAGGCUCUGCAGUA NM_022832  935 FLJ12552 CAAGAGAGUAACUGAAAGA NM_022832  936 FLJ12552 GAGCAGAAUACAUCCAUUA NM_022832  937 FLJ12552 GAAACAGGGUGAAGAGAAG NM_022832  938 FLJ12552 CAAACAAGAAGCCCAGAAA NM_022832  939 FLJ12552 GUAGCAAAGAUGAAGAUUU NM_022832  940 FLJ12552 UGGAGCAGCUGCACAGAUA NM_022832  941 FLJ14981 GGAGUGAGGUCGUGGGUUA NM_032868  942 FLJ14981 CCAUCGAAGAGGAGAUCUA NM_032868  943 FLJ14981 UGGAAGAGGAGGAGGAGGA NM_032868  944 FLJ14981 GGAAGCGGGUGGACAGCAA NM_032868  945 FLJ14981 GGGCUCAGGUAAUAAAGAA NM_032868  946 FLJ14981 AGGAGUUGCUGAUGGAAGA NM_032868  947 FLJ14981 GGGUCUCAGCAGAGGACAA NM_032868  948 FLJ14981 GGACAAGAGUCGGAGACCA NM_032868  949 FLJ14981 AGAAACUGGACAAGUACAA NM_032868  950 FLJ14981 GCAAGAAGCUGGUGAACCC NM_032868  951 FLJ14981 UGAUGGAAGAGGAGGAGGA NM_032868  952 FLJ14981 CGGAUGGGCUCAGGUAAUA NM_032868  953 FLJ14981 GGGCCUCUGUCAAGUACAA NM_032868  954 FLJ14981 AGUACAAAGGCCAGAAACU NM_032868  955 FLJ14981 CUUAAGAUCUCCUUGGCCA NM_032868  956 FLJ14981 AGUCCAAGAUCUCGCCUUU NM_032868  957 FLJ14981 UCAACAAGUUCCAGCCGUU NM_032868  958 FLJ14981 CAGCCAGACGGAAGGAUCA NM_032868  959 FLJ14981 CCGAGAUGCUGCUGGUGGA NM_032868  960 FLJ14981 AGGAGGAGUUGCUGAUGGA NM_032868  961 FLJ14981 CUGCAGGGCUCCAGCAAUG NM_032868  962 FLJ14981 AGAUGCUGCUGGUGGAGUU NM_032868  963 FLJ14981 CAAGUACAAAGGCCAGAAA NM_032868  964 FLJ14981 ACGCACAGAUGGACUACCA NM_032868  965 FLJ14981 UCGACAAGCUUAAGAUCUC NM_032868  966 FLJ14981 ACACCUACCUCGACAAGCU NM_032868  967 FLJ14981 GGUGGAAGUAACAUCCUUU NM_032868  968 FLJ14981 GGAGCCAGGAGCACACCUA NM_032868  969 FLJ14981 GGAUGGGCUCAGGUAAUAA NM_032868  970 FLJ14981 GCUCAGGUAAUAAAGAAAC NM_032868  971 FLJ20113 ACGAUAUCCUCUACAAAUA NM_017670  972 FLJ20113 GAUCAAGGACCUCCACAAA NM_017670  973 FLJ20113 GGUUGUAAAUGGUCCUAUU NM_017670  974 FLJ20113 AGGAGUAUGCUGAAGAUGA NM_017670  975 FLJ20113 CAAUUGAGGAUUUCCACAA NM_017670  976 FLJ20113 GCAAGGAGAGCGACCACAU NM_017670  977 FLJ20113 CCUAUCUACUCCUGAGCUU NM_017670  978 FLJ20113 UGGAGGCACUGCUGGAUGA NM_017670  979 FLJ20I13 UCUAUGGGAUCCUGGAAGU NM_017670  980 FLJ20113 ACUACGAUAUCCUCUACAA NM_017670  981 FLJ20113 GACCGAAUUCAGCAAGAGA NM_017670  982 FLJ20113 CAACAUCUAUCAACAGAAG NM_017670  983 FLJ20113 GCCAGGCGCUAGACAUGUA NM_017670  984 FLJ20727 AGAUAAAGAUGGUGAACAA NM_017944  985 FLJ20727 CGAGAGAAGCUUAGUGAAA NM_017944  986 FLJ20727 GGAUAAGACAUUAAAGGAA NM_017944  987 FLJ20727 CAACAUGUCAGCAGGAUAA NM_017944  988 FLJ20727 GGAUGGAGCACCAAAUAAA NM_017944  989 FLJ20727 GAGAAGUGAUGGUGAAAGU NM_017944  990 FLJ20727 GGAAUCAUGUUGUGCACUA NM_017944  991 FLJ20727 CCAUUUACCUGCUGAAACA NM_017944  992 FLJ20727 CAGUAGAAAUGGCUUAUAA NM_017944  993 FLJ23251 GGGAGAAGGACAAGGCAUA NM_024818  994 FLJ23251 GAACAUACUCUGAGGAACA NM_024818  995 FLJ23251 GCAUACAGCUUAUUGAUUA NM_024818  996 FLJ23251 CAAAGGAUAUUGUAGGAUA NM_024818  997 FLJ23251 AGACUUACCUGAAGGAAUU NM_024818  998 FLJ23251 GCUCAGAGGUGGUGGAUUC NM_024818  999 FLJ23251 AAGAAAACCUCAAAGGAUA NM_024818 1000 FLJ23251 GAUUAGAGCUGGCAAGCAU NM_024818 1001 FLJ23251 GGACAAAUCUGAUCCUGUA NM_024818 1002 FLJ23251 GGACAUGGACAAUAAAGUA NM_024818 1003 FLJ23251 AGUAUAUGAUCCUCAGAUA NM_024818 1004 FLJ23251 UGUAAGCGACUAUGAGAAA NM_024818 1005 FLJ23251 GGACAAGGCAUACAGCUUA NM_024818 1006 FLJ23251 GGAACUAGCCAAUAUGAAU NM_024818 1007 FLJ23251 GAAAUAACAUCCUCUCAAA NM_024818 1008 FLJ23251 AUGAGGACAUGGACAAUAA NM_024818 1009 FLJ23277 CAGAAAGGAUGGAGAACAU NM_032236 1010 FLJ23277 CAAUAAAGCAUGAAAGUGA NM_032236 1011 FLJ23277 GGUGAAUGGUAUAAGUUUA NM_032236 1012 FLJ23277 CAUCAGACUUGAAGGAAAU NM_032236 1013 FLJ23277 AGACGAAACUGCAAAGGAA NM_032236 1014 FLJ23277 GUAGAAGAGUGGCGGAAAU NM_032236 1015 FLJ23277 CCAAAUGCCUUAUGUCAAA NM_032236 1016 FLJ23277 GAAAUUACAACUAGGGAUU NM_032236 1017 FLJ23277 GGAAGAAAAUGAAGCCUUA NM_032236 1018 FLJ23277 GCAAGAUGGUGAUGCAGAA NM_032236 1019 FLJ23277 GAUGUAAACCCUUCAGAAA NM_032236 1020 FLJ23277 GAGGAGUGGUGUAUUGAAA NM_032236 1021 FLJ23277 GAACAAAGCAACGGAAAGA NM_032236 1022 FLJ23277 GCAUAUUGCGUCUGAAGAA NM_032236 1023 FLJ25157 GCAAGAACCAGAAAGAGAA NM_152653 1024 FLJ25157 AGAAGGAACUUGCAGAAAU NM_152653 1025 FLJ25157 CCAAAGGAGACAACAUUUA NM_152653 1026 FLJ25157 CUGUAGUGCUGGACCCAAA NM_152653 1027 FLJ25157 ACAAAGAGUUGAUGACAGU NM_152653 1028 FLJ25157 CCAACAGAGCAGAGCAUGA NM_152653 1029 FLJ25157 GAAUGGAGGUCAACUAUAU NM_152653 1030 FLJ25157 CGAUGGAGAUCAACGUGAA NM_152653 1031 FLJ25157 CCACACAGUACAUGACCAA NM_152653 1032 FLJ25157 GCUGCUAAAUUGUCAACUA NM_152653 1033 FLJ25157 GAUGACAGUCCAAGCACUA NM_152653 1034 FLJ25157 GGAGACAACAUUUAUGAAU NM_152653 1035 FLJ25157 CUAAAAGAAUUCAGAAGGA NM_152653 1036 FLJ25157 GAAGGAACUUGCAGAAAUC NM_152653 1037 FLJ25157 CAGAAGGAACUUGCAGAAA NM_152653 1038 FLJ25157 UCAGCAAGAACCAGAAAGA NM_152653 1039 FLJ25157 CCACUGAGGCACAAAGAGU NM_152653 1040 FLJ25157 UCAGAAGGAACUUGCAGAA NM_152653 1041 FLJ25157 CAAGAAUCUAUCACUGUAA NM_152653 1042 FLJ25157 GAUGGAGAUCAACGUGAAA NM_152653 1043 FLJ25157 UAUGAAUGGAGGUCAACUA NM_152653 1044 FLJ25157 GCACAAAGAGUUGAUGACA NM_152653 1045 FLJ25157 UCACCAGACUAUCCGUUUA NM_152653 1046 FLJ25157 AGAUCAACGUGAAAGUGUU NM_152653 1047 FLJ25157 ACAAGAAUCUAUCACUGUA NM_152653 1048 FLJ25157 CAACUGGAGUCCGGCUUUA NM_152653 1049 FLJ25157 GAGAUCAACGUGAAAGUGU NM_152653 1050 FLJ25157 UGAAUGGAGGUCAACUAUA NM_152653 1051 FLJ25157 GCAAAACCGCUGCUAAAUU NM_152653 1052 FLJ25157 CAACUAGUGCUAAAAGAAU NM_152653 1053 FLJ30626 GAAGAUGGUUGCAGAGGAA NM_153210 1054 FLJ30626 GCAAGGAAACUCAAGGAAA NM_153210 1055 FLJ30626 CAAGGAAACUCAAGGAAAA NM_153210 1056 FLJ30626 GUGAAAGGCAGAAGCAUUA NM_153210 1057 FLJ30626 CGUGAAAGGCAGAAGCAUU NM_153210 1058 FLJ30626 ACAUCAAGCUUCCCAGAAA NM_153210 1059 FLJ30626 CAAUAUAGAUCUUCCUUGA NM_153210 1060 FLJ30626 GAGAACAGGAGGAAUGAGA NM_153210 1061 FLJ30626 GCACUGGGCAUGUCACAAA NM_153210 1062 FLJ30626 GGCAGAAGCAUUAGCAUGA NM_153210 1063 FLJ30626 GGGCUUAUAUCCUGUUCUA NM_153210 1064 FLJ30626 AGAGGGAGAUAAUGUGUAU NM_153210 1065 FLJ30626 GAAGGCUGCUCGAGGAACA NM_153210 1066 FLJ30626 GGAUGGUGAAGCUGAGUUU NM_153210 1067 FLJ30626 GCAGCAGGCUAGCAGGUUU NM_153210 1068 FLJ30626 GCACUGCGGGUGAGGAUGA NM_153210 1069 FLJ37318 GCUCAGUCGUCAAUGUAAA NM_152586 1070 FLJ37318 GGGAAGAGUCCACUGAACA NM_152586 1071 FLJ37318 GGAAGAGUCCACUGAACAU NM_152586 1072 FLJ37318 AAAGAUGAAUCCAUGGUAU NM_152586 1073 HP43.8KD GGUAAUAGAUUUUCCAGAA NM_032557 1074 HP43.8KD GGAAGUAAUUUUCGUGCUA NM_032557 1075 HP43.8KD CAAAAUGCAUCAUGGAAAA NM_032557 1076 HP43.8KD CCAGUGAAGAGAAGAUUAA NM_032557 1077 HP43.8KD CCAAUGGAUUUGAUGACAA NM_032557 1078 HP43.8KD UGUUUGAACUGCAGGAGUA NM_032557 1079 HP43.8KD AAAGAGAGCUGCGGGAAUA NM_032557 1080 HP43.8KD UAUACAAGAUGGUGGUCUA NM_032557 1081 HP43.8KD UUAGAAGAAUUCAGAGGAA NM_032557 1082 HP43.8KD GAGUAUAUCUUCUGUGGUU NM_032557 1083 HP43.8KD GAUCAGAAGUAUCAUGUGA NM_032557 1084 HP43.8KD AGACCCACCUCUACAGAAA NM_032557 1085 HP43.8KD GAUGAAGCUUCCUGCACAA NM_032557 1086 HP43.8KD UCACACAAGCCUUCUGAAA NM_032557 1087 HP43.8KD AGAAGAACCAGUAGUUUAU NM_032557 1088 HSA243666 GGACAUAAAGAAAGGGAAU NM_017582 1089 HSA243666 AUGCUGAGGUUGAGAUAAA NM_017582 1090 HSA243666 AGAGAAACUUGGAGCUGAA NM_017582 1091 HSA243666 CAGUCGAACUCGUGAAUGA NM_017582 1092 HSA243666 GAGAUAAAGACGGGACAUA NM_017582 1093 HSA243666 GGAUGGUGAUCAUUGGUAA NM_017582 1094 HSA243666 CCAAAGGAUGAAACAAAUA NM_017582 1095 HSA243666 CUAGAAAGGGUUAGCAUUU NM_017582 1096 HSA243666 UACCAAAGGAUGAAACAAA NM_017582 1097 HSA243666 GCAACAUCACGGAGUCAUA NM_017582 1098 HSA243666 ACACAGAAGACUUAGAUCA NM_017582 1099 HSA243666 GCAUGGAACUUCUCACCAA NM_017582 1100 HSA243666 AGAUAAAGACGGGACAUAA NM_017582 1101 HSA243666 CUGAAACGAUGGUGUUAAU NM_017582 1102 HSA243666 CAACAAAUCUCAAUACAGU NM_017582 1103 HSA243666 AGAAAGGGUUAGCAUUUUA NM_017582 1104 HSA243666 GGGAAAUUAUGGAUUCUUU NM_017582 1105 HSA243666 CCAAAGAUGGCCAAGUGAA NM_017582 1106 HSHIN1 GGAAGUAGCUGAUGAAGAU NM_017493 1107 HSHIN1 GGGUAGGACAAGUGGAAAU NM_199324 1108 HSHIN1 UCGAGAGAACAGAGAGAAA NM_017493 1109 HSHIN1 GAGAGAACAGAGAGAAAUU NM_017493 1110 HSHIN1 GAUGAAGAUAACAGUGAAA NM_017493 1111 HSHIN1 AGAGAAAUUUGAAGCGUUU NM_017493 1112 HSHIN1 GGAUGACAGUUGCAAGUAA NM_017493 1113 HSHIN1 AUGAAUUGCUGUAUGAGAA NM_017493 1114 HSHIN1 GAGAGAAAUUUGAAGCGUU NM_199324 1115 HSHIN1 AGAAGGAUCAUUUGAAGAA NM_017493 1116 HSHIN1 UAUCAGAUUCAGAGGAUGA NM_017493 1117 HSHIN1 UCACAUACCCAGUAAUGAA NM_017493 1118 HSHIN1 UGCCAUACAAGGAAAGUUA NM_017493 1119 HSHIN1 UGGAAGUAGCUGAUGAAGA NM_017493 1120 HSHIN1 ACAGGAAUGGGUAGGACAA NM_017493 1121 HSHIN1 GGUAGGACAAGUGGAAAUA NM_017493 1122 HSHIN1 CUUCGAGAGAACAGAGAGA NM_017493 1123 HSHIN1 GAACAGAGAGAAAUUUGAA NM_017493 1124 HSHIN1 CGUUGGAAGUAGCUGAUGA NM_017493 1125 HSHIN1 GGGACUGUUUGCUUUGAAA NM_017493 1126 HSHIN1 CAUACCCAGUAAUGAAAUA NM_017493 1127 HSHIN1 CUUAUGUACAGGAAAGAUU NM_199324 1128 HSHIN1 CUGAUGAAGAUAACAGUGA NM_017493 1129 HSHIN1 UCACUAUCUUCGAGAGAAC NM_017493 1130 HSHIN1 AAUAUCAGAUUCAGAGGAU NM_017493 1131 HSHIN1 GUGUAUCCCAUAAAGUAUA NM_017493 1132 HSHIN1 UGAUGAAGAUAACAGUGAA NM_017493 1133 HSHIN1 CGAGAGAACAGAGAGAAAU NM_017493 1134 HSHIN1 AAGUAGCUGAUGAAGAUAA NM_199324 1135 HSHIN1 CUUCACAAGUAACAGAAAA NM_199324 1136 KIAA0063 CAGAAGAGGUAGAGGCUCA NM_014876 1137 KIAA0063 GCAAAUGGCACUUGAAAGA NM_014876 1138 KIAA0063 GGACAAAAGAGAAGCCAAA NM_014876 1139 KIAA0063 GGAAAGGAGACAAGGCCAA NM_014876 1140 KIAA0063 CGGCAGAGUUUUAUAAUGA NM_014876 1141 KIAA0063 AGAAGAGCAUGCUGGGAAA NM_014876 1142 KIAA0063 GCAUGUUGAUCCUGAGCAA NM_014876 1143 KIAA0063 UGAAGGACCCAGAGCAUAA NM_014876 1144 KIAA0063 CGUUAUAUCUUCUCAGCAA NM_014876 1145 KIAA0063 GCAAAGACGCUUAAACAUU NM_014876 1146 KIAA0063 AGACAGGCUUCUUGGAGUA NM_014876 1147 KIAA0063 ACAAAUCUACCAUGAGAAA NM_014876 1148 KIAA0063 AAACAUCAUUUGCGAGGAA NM_014876 1149 KIAA0063 GGAUAUGCAAAGACGCUUA NM_014876 1150 KIAA0063 CCACAAAUCUACCAUGAGA NM_014876 1151 KIAA0063 AUAAAGGUCUCUCAGGAAA NM_014876 1152 KIAA0063 CAUGGACACCAGAGAAUAA NM_014876 1153 KIAA0063 UCACUAACGUCAUGGGCUU NM_014876 1154 KIAA0063 CAUAAAGGUCUCUCAGGAA NM_014876 1155 KIAA0063 CCAAGCGGCUACUGCGUUA NM_014876 1156 KIAA0063 AAGAAGAGCAUGCUGGGAA NM_014876 1157 KIAA0063 GGAAACUCCUCUCCACAAA NM_014876 1158 KIAA0063 UGGCAGCACUUCAGACCAA NM_014876 1159 KIAA0063 AAAUCUACCAUGAGAAACA NM_014876 1160 KIAA0063 UGACAGUGGUAGCAAAAUA NM_014876 1161 KIAA0063 GCAACUACGAUGUGAAUGU NM_014876 1162 KIAA0063 GGAAAGUAUUGUGAAGACA NM_014876 1163 KIAA0063 GGGAGGGAAUCCUAGCUUA NM_014876 1164 KIAA0063 CGGGAUACGCUGCAAGAGA NM_014876 1165 KIAA0063 CCACUGGCACUGUCAGAUA NM_014876 1166 KIAA0710 CAAGAUGGCAGUAAAGAAA NM_014871 1167 KIAA0710 AGGAGCAGGUGGUGGAUUA NM_014871 1168 KIAA0710 GAAUUGACCCAGAUGGAAA NM_014871 1169 KIAA0710 GGGUAUACAUUGUGCCUUU NM_014871 1170 KIAA0710 GGUCACAGAUGGUGCUAUU NM_014871 1171 KIAA0710 CCAAACAAGUCCCAAGAAU NM_014871 1172 KIAA0710 UGACCCAGAUGGAAAGUAA NM_014871 1173 KIAA0710 CACAGUAGUUCAAGACUUA NM_014871 1174 KIAA0710 CAUCAAAUAUUCCAAGCUA NM_014871 1175 KIAA0710 CCACAGUAGUUCAAGACUU NM_014871 1176 KIAA0710 GAUACAACCUGAACAUCAA NM_014871 1177 KIAA0710 GCUAUUAAUUGAACUGGAA NM_014871 1178 KIAA0710 CCUGAUGGCUACUGUGGUA NM_014871 1179 KIAA0710 AAGAACAACCUCAAGUAUA NM_014871 1180 KIAA0710 GAUGGAAAGUAAUUGGUAU NM_014871 1181 KIAA1203 GGUCAGUGUUGUUGGAAUA NM_020718 1182 KIAA1203 AGAAGGAAAUCUUGGAGAA NM_020718 1183 KIAA1203 UGAAAUUUGGCUUGGAUUA NM_020718 1184 KIAA1203 AGAAAGGAGUGAAGAUGAU NM_020718 1185 KIAA1203 CAGAUUGUGUUAACAGAAA NM_020718 1186 KIAA1203 UGGAGAAGAUGAAGUAUUU NM_020718 1187 KIAA1203 GAACCAAGCGACAGUCAUA NM_020718 1188 KIAA1203 CAUCGUUCCUUUUGUGAUA NM_020718 1189 KIAA1203 AGAAAGUGUUCGUCUGCAA NM_020718 1190 KIAA1203 GAAGCAGUGUCUAUGGAAA NM_020718 1191 KIAA1203 GUAUAUUCCUGAUGCAGAA NM_020718 1192 KIAA1203 UGGCACUGCUCAUGUGAAA NM_020718 1193 KIAA1203 CUUUGAGACUCCCGAAAUA NM_020718 1194 KIAA1203 GAGAAAGGAGUGAAGAUGA NM_020718 1195 KIAA1203 UGAAGAUGAUGGAGGCUUU NM_020718 1196 KIAA1203 GACAAGGAGACAAGAGAUU NM_020718 1197 KIAA1203 GCAGGGAAGCAUUACGUUA NM_020718 1198 KIAA1203 CCUCAAACCUGCACUUUAU NM_020718 1199 KIAA1203 CAGGGAAGCAUUACGUUAA NM_020718 1200 KIAA1203 UGUAGUGUAUCAAGGCAAA NM_020718 1201 KIAA1203 CAUGAAAGCGACUGCAUUU NM_020718 1202 KIAA1203 CGUCAGAGUUUGUCAUCCA NM_020718 1203 KIAA1453 CCGUAUAUGUCCCAGAAUA NM_025090 1204 KIAA1453 GCACACAGCCACAGGUGAA NM_025090 1205 KIAA1453 GAACAUCGGCAAUGGGAUU NM_025090 1206 KIAA1915 GGACUGAGAAACAGAGCAA XM_055481 1207 KIAA1915 GGUUAUAAGUGAGGAAAUU XM_055481 1208 KIAA1915 AAGCUAAAUACCAGAGUUA XM_055481 1209 KIAA191S GUUAGAGGCUUCAGUGUUA XM_055481 1210 KIAA1915 AAAUGAAGAUAAAGGGACA XM_055481 1211 KIAA1915 GGAUAAAGAAACACCAAAU XM_055481 1212 KIAA1915 GGUUAGAAUUCAAGUAGUU XM_055481 1213 KIAA1915 GAAAAGACAAGAUGGAUAA XM_055481 1214 KIAA1915 AGGAAAGCCAUGAGGAAGA XM_055481 1215 KIAA1915 CAGAAAAGAUGCAGUAGAA XM_055481 1216 KIAA1915 GUACAGGACUACAGUGUGA XM_055481 1217 KIAA1915 AAAGAAGAGAAGAGGAAAA XM_055481 1218 KIAA1915 UGAAAAGACAAGAUGGAUA XM_055481 1219 KIAA1915 AGAGGAAAGCCAUGAGGAA XM_055481 1220 KIAA1915 GUGCAAAGUUCAUUGGGAU XM_055481 1221 KIAA1915 GCCACAAACAGUUGACAAA XM_055481 1222 KIAA1915 GCCAAAUGGUAGAGGAAAG XM_055481 1223 KIAA1915 ACUCAGAAGUUGAUAAAGU XM_055481 1224 KIAA1915 CAAAGGACUUAGAAGGACA XM_055481 1225 KIAA1915 GAAAUAAUCCCUUACCAUA XM_055481 1226 KIAA1915 GGCCAUAAUCUUCAAGUUA XM_055481 1227 KIAA1915 CUGCUGAGGAGUUGGCAAA XM_055481 1228 KIAA1915 ACAGAGCAAUGGUGACAAA XM_055481 1229 KIAA1915 GCUUUAUGGCUGAAGAAUU XM_055481 1230 KIAA1915 UCAAAUGCGGUCUGGAUAA XM_055481 1231 KIAA1915 CUACAAAACCAGCCAGUUA XM_055481 1232 KIAA1915 GAUAAAGGGACAAAGGCAU XM_055481 1233 KIAA1915 UGAGGAAGACUCUGAGCAA XM_055481 1234 KIAA1915 CAACCAAGAGAAUGGAGUA XM_055481 1235 KIAA1915 AGUGAAGAGUUAUGCAAGA XM_055481 1236 LOC161725 GCAAGAACGGCAAGGACAA NM_130901 1237 LOC161725 CAGCAGACGCAGCAGAAUA NM_130901 1238 LOC161725 GAUACAAUGUUAAGAGACU NM_130901 1239 LOC161725 GCAAGGACAAGGAGAAGGA NM_130901 1240 LOC161725 GUUCUACCUUCGAGGAUUU NM_130901 1241 LOC161725 ACAAGGAGAAGGAGAAGCA NM_130901 1242 LOC161725 AGAAGCAGCGCAAGGAGAA NM_130901 1243 LOC161725 AGAGAGACCAGCAAAGAGA NM_130901 1244 LOC220213 CAAACAAACUCAAGUGCAA XM_166659 1245 LOC220213 CGACGAAGAACUUGCCAAA XM_166659 1246 LOC220213 GAGUAAUGGCCACAGGAAA XM_166659 1247 LOC220213 AGACAGAACACCAGCUAAU XM_166659 1248 LOC220213 UGGAGGAGCACUUGACAAA XM_166659 1249 LOC220213 CCAGCUAAUGAAAGAGUUA XM_166659 1250 LOC220213 AUGAAAGAGUUAAGCGUGA XM_166659 1251 LOC220213 GGGCAGAUGCUGAAUGUGA XM_166659 1252 LOC220213 CCUAAGUGAUACUGCAUUU XM_166659 1253 LOC220213 UGGAGAAGCAGGACAAGUA XM_166659 1254 LOC220213 GCAAAGGAAACGCGACGAA XM_166659 1255 LOC220213 GGAUGGGCCCUAAGUGAUA XM_166659 1256 LOC220213 GGUCAGAGGUGCAAAGUUG XM_166659 1257 LOC220213 GAGGAUUCCCUGAGGCCUA XM_166659 1258 LOC220213 GCGAAGAGCACUUGGCGGA XM_166659 1259 LOC220213 CAACAGAUGCUCAACAAAU XM_166659 1260 LOC220213 ACGAGAAGCUGGCCCUAUA XM_166659 1261 LOC220213 GGGAGCAGACGGUGCACUA XM_166659 1262 LOC220213 GAGGAGCACUUGACAAAGA XM_166659 1263 LOC220213 AGGUGGAGAAGCAGGACAA XM_166659 1264 LOC220213 CAGUUAGGCUGGAGAAAUG XM_166659 1265 LOC220213 UGGCCGAGGUGGAGAAGCA XM_166659 1266 LOC220213 AAACUCAAGUGCAAAGGAA XM_166659 1267 LOC220213 AAGGAAACGCGACGAAGAA XM_166659 1268 LOC220213 GGAGAAAUGAGACAGAACA XM_166659 1269 LOC220213 GACAACUGGUGCAAACAAA XM_166659 1270 LOC220213 GCUCAGUAACGGACACUAU XM_166659 1271 LOC220213 ACACUAUGAUGCUGUAUUU XM_166659 1272 LOC220213 CCACCUACCUUGAGUAAUG XM_166659 1273 LOC220213 GAAAUGAGACAGAACACCA XM_166659 1274 MGC10702 AGAAAUAACUCCCAAACAA NM_032663 1275 MGC10702 AGGCAACAAUUUAGAAGAA NM_032663 1276 MGC10702 GUGCAAGUCUGAAGAAUGA NM_032663 1277 MGC10702 GAAAGAAAGAAGCGUAGAA NM_032663 1278 MGC10702 CCAAGAAGUUACUGAUGAU NM_032663 1279 MGC10702 GGAAGACUCACUAGUAAUA NM_032663 1280 MGC10702 ACAGGAUGCUCACGAAUUA NM_032663 1281 MGC10702 CAAAUUACCUGCCGCACAA NM_032663 1282 MGC10702 GGAGCAGCAGUCAGAAAUA NM_032663 1283 MGC10702 GGGAGGUACCUUUGUCUAA NM_032663 1284 MGC10702 CAGCAGGAAUAUAUGUUAU NM_032663 1285 MGC10702 UGACAACUGUACAAAGAUU NM_032663 1286 MGC10702 CAACACAACCCUAAACUGA NM_032663 1287 MGC10702 AGGUGGUUCUGUUGUGUUA NM_032663 1288 MGC10702 AUGGAAGACUCACUAGUAA NM_032663 1289 MGC10702 CCACACCAGUUCUGAAUCA NM_032663 1290 MGC14793 UGAUAUUGCUGUAGGUUUA NM_032929 1291 MGC14793 CAUGAAACUUUGUGAAGAA NM_032929 1292 MGC14793 GGUGAAAGAUCCAACUAAA NM_032929 1293 MGC14793 GGAAAUGGAGACACAGAAA NM_032929 1294 MGC14793 AGAAAGUACCGUAAGAUAA NM_032929 1295 MGC14793 GCAAAUAGAGUUUAAGUGA NM_032929 1296 MGC14793 GAGCAAUAGCUGAGAAUCU NM_032929 1297 MGC14793 GCACAGACUUAUACUCUUA NM_032929 1298 MGC14793 GUGAAUUUCUCAAGGUAUU NM_032929 1299 MGC14793 GAUCAAAGAAAGUAGUACA NM_032929 1300 MGC14793 GGAGGAAAAUGCAGAAAUU NM_032929 1301 MGC14793 UAGAAAGUACCGUAAGAUA NM_032929 1302 MGC14793 GCUCUAUGCUUUAUGAAAA NM_032929 1303 MGC14793 AUAAGGAAAUGGAGACACA NM_032929 1304 MGC14793 CUCAGAAUGUUUAGAAGAA NM_032929 1305 MGC14793 AAAUGGAGACACAGAAAUU NM_032929 1306 MGC14793 CGUGAAUCAUGUAAAGAGA NM_032929 1307 MGC14793 GCUCAGAAUGUUUAGAAGA NM_032929 1308 MGC14793 GAGAAUCUGUGGUCAGUUU NM_032929 1309 MGC14793 GGGUGAAAGAUCCAACUAA NM_032929 1310 MGC14793 GAGAAAGCCAAAAGAAGUA NM_032929 1311 MGC14793 CAGCUUAUCCUCAUAUAUA NM_032929 1312 MGC14793 UGAGGCAAAUAGAGUUUAA NM_032929 1313 MGC14793 UCUAGAAAGUACCGUAAGA NM_032929 1314 MGC14793 GCCUGGAAAUAAACACAUA NM_032929 1315 MGC14793 GAACAGAGCCCCAUUGUAU NM_032929 1316 MGC14793 UUACUGAUCUGAUGAAUGA NM_032929 1317 MGC14793 UGUUACAGCUCUAUGCUUU NM_032929 1318 MGC14793 GUAAUACCAUAAAGUGAGA NM_032929 1319 MGC14793 CAGAAUGUUUAGAAGAAAG NM_032929 1320 MJD CCAAAGAGGCAUUCAGCAA NM_004993 1321 MJD CAAACAAAAUGAUGGGAAA NM_030660 1322 MJD CUUUAGAAACUGUCAGAAA NM_004993 1323 MJD GUUCAACAGUCCAGAGUAU NM_030660 1324 MJD UCAAAGAGAUGAGGAAAUA NM_030660 1325 MJD GCACUAAGUCGCCAAGAAA NM_004993 1326 MJD ACGAAGAUGAGGAGGAUUU NM_030660 1327 MJD GAAACAGCCUUCUGGAAAU NM_030660 1328 MJD CCGCAGGGCUAUUCAGCUA NM_004993 1329 MJD CAAGGUAGUUCCAGAAACA NM_004993 1330 MJD CAAAUUAACCUUUCAGGAA NM_030660 1331 MJD CAGGAAUGUUAGACGAAGA NM_004993 1332 MJD AGUAAUGGUUCUAGAAGGA NM_004993 1333 MJD AAUUACAACAGGAAGGUUA NM_030660 1334 MJD CGAGAAGCCUACUUUGAAA NM_030660 1335 MJD UGACAUGGAAGAUGAGGAA NM_030660 1336 MJD UGGAGAAGAAUUAGCACAA NM_030660 1337 MJD CUUGACGGGUCCAGAAUUA NM_030660 1338 MJD CAACAGAUGCAUCGACCAA NM_004993 1339 MJD ACUAAGUCGCCAAGAAAUU NM_004993 1340 MJD GAUCACAACUUUUCUGCUA NM_004993 1341 MJD GCUCAACAUUGCCUGAAUA NM_004993 1342 MJD AGACCUGGAACGAGUGUUA NM_030660 1343 MJD GGUAAUGUGUCAAAGAGAU NM_030660 1344 MJD GGAAGAGACGAGAAGCCUA NM_030660 1345 MJD CCAAGAAAUUGACAUGGAA NM_030660 1346 MJD UGAAAUCAGCCUUGCACAA NM_030660 1347 MJD ACAGGAAGGUUAUUCUAUA NM_004993 1348 MJD AAGAAAUUGACAUGGAAGA NM_030660 1349 MJD AGGUAGUUCCAGAAACAUA NM_030660 1350 NY-REN-60 GGGAAGAAAUGGAAAGAAU NM_032582 1351 NY-REN-60 GCUAAGAUCUCAAGUAAAA NM_032582 1352 NY-REN-60 UCUCAAAGGCUGCGCAUUA NM_032582 1353 NY-REN-60 AGGAAAGGGUUGUAGAUGA NM_032582 1354 OTUB1 CCGACUACCUUGUGGUCUA NM_017670 1355 OTUB1 CCGAAUUCAGCAAGAGAUU NM_017670 1356 OTUB1 AGACCAGGCCUGACGGCAA NM_017670 1357 OTUB1 CUGCCAAGAGCAAGGAAGA NM_017670 1358 OTUB1 AGGUGGAGCCCAUGUGCAA NM_017670 1359 OTUB1 GAGCAGGUGGAGAGGCAGA NM_017670 1360 OTUB1 AGGAAGACCUGGUGUCCCA NM_017670 1361 OTUB1 CGGCCUGGACACUACGAUA NM_017670 1362 OTUB1 AAGAGAUUGCUGUGCAGAA NM_017670 1363 OTUB1 AGAUCAAGGACCUCCACAA NM_017670 1364 OTUB1 UCUAUCAACAGAAGAUCAA NM_017670 1365 OTUBI ACAAGGAGUAUGCUGAAGA NM_017670 1366 OTUB1 CAAGGAGUAUGCUGAAGAU NM_017670 1367 OTUB1 GGAGUAUGCUGAAGAUGAC NM_017670 1368 OTUB1 CCACCAAUCCGCACAUCUU NM_017670 1369 OTUB1 GGCCUGGACACUACGAUAU NM_017670 1370 OTUB1 CCGAAGGUGUUAACUGUCU NM_017670 1371 POH1 CAAUAAGGCUGUAGAAGAA NM_005805 1372 POH1 GGCAUUAAUUCAUGGACUA NM_005805 1373 POH1 CUGAACAGCUGGCAAUAAA NM_005805 1374 POH1 CAGAAGAUGUUGCUAAAUU NM_005805 1375 POH1 ACAAUAAGGCUGUAGAAGA NM_005805 1376 POH1 AAGGAAAGGUUGUUAUUGA NM_005805 1377 POH1 CCAGAAAUAUGGACAGACU NM_005805 1378 POH1 GUUUGACACUUCAGGACUA NM_005805 1379 POH1 CUUAAGAGUUGUAGUUACU NM_005805 1380 PRPF8 AGGAGAAGCUGCAGGAGAA NM_006445 1381 PRPF8 GGGCCAAGUUCCUGGACUA NM_006445 1382 PRPF8 GGAUAUGGCCGGAGUGUUU NM_006445 1383 PRPF8 UGGCAAAGACAGUAACAAA NM_006445 1384 PRPF8 GCUCAAAAGAAGAGGUAUU NM_006445 1385 PRPF8 UGACAGACUUGGUGGAUGA NM_006445 1386 PRPF8 CCAAGAUCAUGAAGGCAAA NM_006445 1387 PRPF8 CAACAUGAAAUAUGAGCUA NM_006445 1388 PRPF8 GGAUCAAGGUCGAGGUGCA NM_006445 1389 PRPF8 CGGAUGAUGAUGAGGAAUU NM_006445 1390 PRPF8 GAUGAAGACUGGAAUGAAU NM_006445 1391 PRPF8 GGAAAUUGAGACAGUACAA NM_006445 1392 PRPF8 CAGAAAUACUGGAUUGACA NM_006445 1393 PRPF8 AGGAAUGAGCCAUGAAGAA NM_006445 1394 PRPF8 GCAGAUGGAUUGCAGUAUA NM_006445 1395 PRPF8 AACCAAGGAAAGAAAGAAA NM_006445 1396 PRPF8 ACACAUCACUGGAGCCAUU NM_006445 1397 PRPF8 ACAAAGAGUUCUACCACGA NM_006445 1398 PRPF8 GAUUAAGCCUGCAGACACA NM_006445 1399 PRPF8 GGACAUGAACCAUACGAAU NM_006445 1400 PRPF8 CCAAAUUGCAGGAUACCUA NM_006445 1401 PRPF8 CCAAGAAUGUGCUUAAGAA NM_006445 1402 PRPF8 GAUAAGGGCUGGCGUGUCA NM_006445 1403 PRPF8 CAGACUUGGUGGAUGACAA NM_006445 1404 PRPF8 AGAACAACGUCGUCAUCAA NM_006445 1405 PRPF8 CCUAUAAGCAUGACACCAA NM_006445 1406 PRPF8 CAAUGUAUAUGUAGGCUUU NM_006445 1407 PRPF8 AAGACUGAGUGGAGGGUCA NM_006445 1408 PRPF8 GAAUCUAUGAAGUGGAAGA NM_006445 1409 PRPF8 CGAGUGAAGGCGAGUGCAA NM_006445 1410 PSMD14 GGACAUGAACCAAGACAAA NM_005805 1411 PSMD14 CAAUAAAGAAUGUUGGCAA NM_005805 1412 PSMD14 CUGUAGAAGAAGAAGAUAA NM_005805 1413 PSMD14 CAAUGGAAGUUAUGGGUUU NM_005805 1414 PSMD14 ACAAUGAAUCAGUGGUAAA NM_005805 1415 PSMD14 GGACAGACUUCUUAGACUU NM_005805 1416 PSMD14 UAAAGGAGAUGUUGGAAUU NM_005805 1417 PSMD14 GAUUAUACCGUCAGAGUGA NM_005805 1418 PSMD14 GUAAAGGAGAUGUUGGAAU NM_005805 1419 PSMD14 ACACAAUGAAUCAGUGGUA NM_005805 1420 PSMD14 CAAAUAUUGUCCAGUGUUU NM_005805 1421 PSMD14 GUACUUAUGACCUCAAAUA NM_005805 1422 PSMD14 AAUCAGUGGUAAAGGAGAU NM_005805 1423 PSMD14 CAGCAGAACAAGUCUAUAU NM_005805 1424 PSMD14 GGUCUUAGGACAUGAACCA NM_005805 1425 PSMD14 AAGAAGAGUUGGAUGGAAG NM_005805 1426 PSMD14 GAAGAAGAAGAUAAGAUGA NM_005805 1427 PSMD14 AGAGUUGGAUGGAAGGUUU NM_005805 1428 PSMD14 GAACCAAGACAAACAACUU NM_005805 1429 PSMD14 GGGUUUGAUGCUUGGAGAA NM_005805 1430 PSMD14 CAGAGUGAUUGAUGUGUUU NM_005805 1431 AD1 UGUUAGAGGUGGAGGAUUU NM_006590 1432 AD1 GGACUUUGACUUUGAGAAA NM_006590 1433 AD1 ACAUAAAGGCCAAUGAUUA NM_006590 1434 AD1 UUGGAGAGCUGAUGAGAAA NM_006590 1435 AD1 AGGCAAAUGGUAUGAAUUA NM_006590 1436 AD1 CUGAAGAAGUACACAAGAA NM_006590 1437 AD1 GGAACUACUUUCUGGAAGA NM_006590 1438 AD1 GAAGAAGUACACAAGAAUA NM_006590 1439 AD1 GAGAAGGAAUAUAAGACUU NM_006590 1440 AD1 GGCUGAUGAUGGUAAAUAA NM_006590 1441 AD1 GAGAUAAUGAUGAAACCAA NM_006590 1442 AD1 ACAGAUAAUUCCUUCCAAA NM_006590 1443 AD1 GGAAGAGGCGAGAUAAUGA NM_006590 1444 AD1 GGGAGUAGUUGAAGAACAG NM_006590 1445 AD1 GAGGCGAGAUAAUGAUGAA NM_006590 1446 AD1 GCAAAUGGUAUGAAUUACA NM_006590 1447 AD1 GUAAAUAAGAACACAGAAG NM_006590 1448 AD1 GCAAGCAGAAAGCCAGUAA NM_006590 1449 SBBI54 CCAAGGAGGUGGAGGAGAA NM_138334 1450 SBBI54 UGACCAAGGAGGUGGAGGA NM_138334 1451 SBBI54 GGGAAAGGCCAGCACUUCA NM_138334 1452 SBBI54 CGGCAACUAUGAUGUCAAU NM_138334 1453 SBBI54 GCGAGGUGCUGCUGGUAGU NM_138334 1454 SBBI54 GCAACUAUGAUGUCAAUGU NM_138334 1455 SBBI54 UGGACGGUGUCUACUACAA NM_138334 1456 SBBI54 GGAAAGGCCAGCACUUCAU NM_138334 1457 SBBI54 ACUAUGAUGUCAAUGUGAU NM_138334 1458 SBBI54 CCGCUGCUGCCUCAAUAAA NM_138334 1459 SBBI54 GGAGGCUGCCGAUGAGAUC NM_138334 1460 SBBI54 GCACCGGCAACUAUGAUGU NM_138334 1461 SBBI54 GCUGCUGCCUCAAUAAAUC NM_138334 1462 SBBI54 CAACUAUGAUGUCAAUGUG NM_138334 1463 SBBI54 CCGAUGAGAUCUGCAAGAG NM_138334 1464 SBBI54 GGACGGUGUCUACUACAAC NM_138334 1465 SBBI54 UGCCGCUGCUGCCUCAAUA NM_138334 1466 SBBI54 GGUGGACGGUGUCUACUAC NM_138334 1467 SBBI54 GAGGUGGUGGUGGUAGUGA NM_138334 1468 SBBI54 GAAAGGCCAGCACUUCAUG NM_138334 1469 SENP2 GCGAAUUACUCGAGGAGAU NM_021627 1470 SENP2 CCUCAUGCAUUGUGGGUUA NM_021627 1471 SENP2 GAUUAUAUUUCUAGGGACA NM_021627 1472 SENP2 GGAGUGGACUGGAGCGUAA NM_021627 1473 SENP2 GAACAAACGCUAACUAAUA NM_021627 1474 SENP2 AAGAAGAUGGUGUGGGAAA NM_021627 1475 SENP2 GGUAAAUCUCUUUGAACAA NM_021627 1476 SENP2 GGGUAAAUCUCUUUGAACA NM_021627 1477 SENP2 CAGAGAAGAUGGUCGGAAU NM_021627 1478 SENP2 GGAAGAAGAUGGUGUGGGA NM_021627 1479 SENP2 GGAGAUAUUCAGACAUUAA NM_021627 1480 SENP2 GGACAAACCUAUCACAUUU NM_021627 1481 SENP2 CAAAGAAGUCAGAUGGACA NM_021627 1482 SENP2 GGAAAUCAGUAAUGCCCUA NM_021627 1483 SENP2 AGAGAAGUACCGAAAGUUA NM_021627 1484 SENP2 GAGGAGAUAUUCAGACAUU NM_021627 1485 SENP2 CCACAAAGCCCAUGGUAAC NM_021627 1486 SENP2 GCUGAAACUGGGUAAUAAA NM_021627 1487 SENP2 GGAACAACAUGCUGAAACU NM_021627 1488 SENP2 AAAGAGAGGGACAGAAGAA NM_021627 1489 SENP2 GGAGGAAAGUGUCAAUAAU NM_021627 1490 SENP2 AAAGAGAGAAGUACCGAAA NM_021627 1491 SENP2 GCAAAAUCACGGAGUCAAA NM_021627 1492 SENP2 UUACAGAGGACAUGGAAAA NM_021627 1493 SENP2 UGGAAAAGGAAAUCAGUAA NM_021627 1494 SENP2 GAUGAAAGUAAGACCAAAA NM_021627 1495 SENP2 CAGUAAUGCCCUAGGCCAU NM_021627 1496 SENP2 CAUGAAACCACACGAGAUU NM_021627 1497 SENP2 AAGAGGAAAGAGAGAAGUA NM_021627 1498 SENP2 UGAUGAAAUACCAGCCAAA NM_021627 1499 TAMBP CAGAAGAGCUGAAGGCAGA NM_201647 1500 TAMBP CCAGCUGGGUAGUGCGGUA NM_006463 1501 TAMBP UGGAAUUCUCUGUGGAAAA NM_006463 1502 TAMBP UGUCAUUCCUGAAAAGAAA NM_006463 1503 TAMBP CCAAAGCAGAAGAGCUGAA NM_201647 1504 TAMBP GAAGGUAGACCCUGGCCUA NM_006463 1505 TAMBP AGUGGAGACAUGUGGAAUU NM_006463 1506 TAMBP CCUUCAUCCUCUAUAACAA NM_201647 1507 TAMBP UCACACAACUGUAAGGCCA NM_201647 1508 TNFAIP3 GGGAAGAUUUGAAGACUUA NM_006290 1509 TNFAIP3 GCACCAUGUUUGAAGGAUA NM_006290 1510 TNFAIP3 GAGCAGGAGAGGAAAGAUA NM_006290 1511 TNFAIP3 CAUAUUUGCUCUAGAAGAA NM_006290 1512 TNFAIP3 GCGGAAAGCUGUGAAGAUA NM_006290 1513 TNFAIP3 UCACAAGAGUCAACAUUAA NM_006290 1514 TNFAIP3 CAGCAUGAGUACAAGAAAU NM_006290 1515 TNFAIP3 GCUAAGAAGUUUGGAAUCA NM_006290 1516 TNFAIP3 GGGACGAGCAAGUGCAGAA NM_006290 1517 TNFAIP3 CAGACUUGGUACUGAGGAA NM_006290 1518 TNFAIP3 CAAAGUUGGAUGAAGCUAA NM_006290 1519 TNFAIP3 GGAAUUGCAUCCAAGGUAU NM_006290 1520 TNFAIP3 UACAAGAAAUGGCAGGAAA NM_006290 1521 TNFAIP3 CAAAAGGACAGAAGAGCAA NM_006290 1522 TNFAIP3 ACAAGAAAUGGCAGGAAAA NM_006290 1523 TNFAIP3 GAAAAUGAGAUGAAGGAGA NM_006290 1524 TNFAIP3 CAGAAGAGCAACUGAGAUC NM_006290 1525 TNFAIP3 GCACAAUGGCUGAACAAGU NM_006290 1526 TNFAIP3 GCUCAAGGAAACAGACACA NM_006290 1527 TNFAIP3 AAAAUGAGAUGAAGGAGAA NM_006290 1528 TNFAIP3 CAAUAGGAAGGCUAAAUAA NM_006290 1529 TNFAIP3 CAACUCACUGGAAGAAAUA NM_006290 1530 TNFAIP3 CCAGUAACCAUGAGUAUGA NM_006290 1531 TNFAIP3 UUUGAAAGUGGGUGGAAUU NM_006290 1532 TNFAIP3 GAAUUGCAUCCAAGGUAUA NM_006290 1533 TNFAIP3 AGUACUUAAUGGUGAUAGA NM_006290 1534 TNFAIP3 AGGCUUUGUAUUUGAGCAA NM_006290 1535 TNFAIP3 AAACGAACGGUGACGGCAA NM_006290 1536 TNFAIP3 AGAGAUUUCAUGAGGCCAA NM_006290 1537 TNFAIP3 UCAUUGAAGCUCAGAAUCA NM_006290 1538 TRABID GGGAGAAACUUUAGGAUAU NM_017580 1539 TRABID GGUAAUAGCCAAAGGAGAU NM_017580 1540 TRABID GGAGCUAGGUAAUGAGGAA NM_017580 1541 TRABID GCAUGCAUCUUUUGAGAAA NM_017580 1542 TRABID GGUUGUAGAAGGUGAUUUA NM_017580 1543 TRABID UGUAAUGACCCUAAAGUUA NM_017580 1544 TRABID GGAGAAACUUUAGGAUAUA NM_017580 1545 TRABID CAGCAGAUAUUGAAGAUUU NM_017580 1546 TRABID GAAGAAGAAUCUCCAAUUA NM_017580 1547 TRABID GAAUUUAUCUCCAGUGUUU NM_017580 1548 TRABID GGAAGUAGUCCUUUGAUAU NM_017580 1549 TRABID ACAGAGAACUUUUGUUGAA NM_017580 1550 TRABID CGUUAUAUCUCCUGCCUAU NM_017580 1551 TRABID UCAAACAGCAGAAGACCAA NM_017580 1552 TRABID GGAAGAUGAGGAUGAUGAA NM_017580 1553 TRFP CAGAGAUGGUCUUGGAGAA NM_004275 1554 TRFP GAAGGCAUCUAAAGAGAAA NM_004275 1555 TRFP AGGCACAACUGGUUUGAUA NM_004275 1556 TRFP CCUCAAGAAUGGUAAUUAU NM_004275 1557 TRFP ACUACAAGAUGAAAGACAA NM_004275 1558 TRFP GCAGUCAUGUGCUGAGUUA NM_004275 1559 TRFP UAUGAAGAGUGGAGAAGUU NM_004275 1560 TRFP ACAUGGAACUCUUCAACAA NM_004275 1561 TRFP UCUACAAGGUUAUCAGGAA NM_004275 1562 TRFP UCCUAGAGAUGGAGUAGAA NM_004275 1563 TRFP GUUAAUGGCUUCUGUUACA NM_004275 1564 TRFP GGAUUGUGCUGUAAUAAGA NM_004275 1565 TRFP CCUGUUUGCUGAAGUGAUU NM_004275 1566 TRFP GCUCAGUUCAGUACCAUAA NM_004275 1567 TRFP GUGAAUGUAUGUACUGUAU NM_004275 1568 TRFP GCUAUAAGAUCGAAGUUUG NM_004275 1569 TRFP GAGGUAAUCAGAUGGUCUA NM_004275 1570 TRFP GAAAUAUUCAUCCAGGUUA NM_004275 1571 TRFP GAUCUUAGGGUUAGAAUAC NM_004275 1572 TRFP AGGCCAAACUGCUAUAAGA NM_004275 1573 TRFP AAAGAGAUGCUGGGACAUA NM_004275 1574 TRFP CAAGUCAGGUGGUGGUCAU NM_004275 1575 TRFP GAUCAAAGCAGACUCAUCA NM_004275 1576 TRFP GCAAGAGUGUUCAGCAAAC NM_004275 1577 UBE1 GCUCAGACCUGCAAGAGAA NM_003334 1578 UBE1 GGGAGGAGGACAUCGGUAA NM_003334 1579 UBE1 CGGCAGUGAAGCAGACAUA NM_153280 1580 UBE1 GGUCAAGGCUGUUACCCUA NM_003334 1581 UBE1 CAGCAGAACUGGUAGCCUU NM_153280 1582 UBE1 UUUCAGAAGUACAGGGCAU NM_153280 1583 UBE1 CCUUCUACCUUGUUUGAAA NM_153280 1584 UBE1 CCUUAUACCUUUAGCAUCU NM_003334 1585 UBE1 GGAGGAGGACAUCGGUAAA NM_003334 1586 UBE1 GGAAAUCAGCCCAUGGAGA NM_003334 1587 UBE1 CCAUUGACUUUGAGAAGGA NM_153280 1588 UBE1 GAGAAAUCAUCGUUACAGA NM_153280 1589 UBE1 GCUAUGGUUUCUAUGGUUA NM_153280 1590 UBE1 AGUCAAAUCUGAAUCGACA NM_153280 1591 UBE1 UCAAAGUACCUAAGAAGAU NM_003334 1592 UBE1 AGAAGGAUGAUGACAGCAA NM_153280 1593 UBE1 CAGACAAGCUCCCUGGAUU NM_153280 1594 UBE1 GAAAUGAUCCUCACAGAUU NM_153280 1595 UBE1 GCGUGGAGAUCGCUAAGAA NM_003334 1596 UBE1 UCAAACAGUUCCUCGACUA NM_003334 1597 UBE1 CCUGAAUCCUAAUAAAGAA NM_153280 1598 UBE1 GGUCAAAGUACCUAAGAAG NM_153280 1599 UBE1 UGCAAGAGAAGCUGGGCAA NM_003334 1600 UBE1 UGGCCAAUGCCCUGGACAA NM_003334 1601 UBE1 CAGAAAAUGUCAACCAGUA NM_003334 1602 UBE1 GGGAUGAGUUUGAAGGCCU NM_153280 1603 UBE1 GGGAUGUCACGAAGUUAAA NM_153280 1604 UBE1 CGGCGAGGAUGUCGAGGUU NM_003334 1605 UBE1 GAGUGGACAUUGUGGGAUC NM_003334 1606 UBE1 GAAAUCAGCCCAUGGAGAU NM_153280 1607 UBE1C AGAGAGAGAUUAUGAGCAA NM_003968 1608 UBE1C GCGAGGAGCCGGAGAAGAA NM_003968 1609 UBE1C GCCUAAAGAUAUUGGAAGA NM_003968 1610 UBE1C AAUGAUACCUGGAGAGAGA NM_003968 1611 UBE1C CAUUUGAAGCAGAAAGAAA NM_198197 1612 UBE1C CAGAAGGUUUUAAAGGAAA NM_198197 1613 UBE1C ACAGAAGGUUUUAAAGGAA NM_003968 1614 UBE1C CAUUGGAGCUGGCGGCUUA NM_003968 1615 UBE1C UGAAGUUGCUGCAGAAUUU NM_003968 1616 UBE1C UACAGGAGGUUUUGGAUUA NM_003968 1617 UBE1C GCUAAGAAGUUGAAUCGAU NM_003968 1618 UBE1C GGAGCAGCCUUUUGGAGAA NM_003968 1619 UBE1C GCUGAAUACCUGUGCAUGA NM_003968 1620 UBE1C AAGCAGAAAGAAAGGAAAA NM_003968 1621 UBE1C GAAGCAGAAAGAAAGGAAA NM_003968 1622 UBE1C GCUGAUAUCUCUUCUAAAU NM_003968 1623 UBE1C CAAUAGUGCUUCUCUGCAA NM_003968 1624 UBE1C AGAGAGAGCAUCACAAUAU NM_003968 1625 UBE1C GGUGUUACGUAUAGGCUCA NM_198195 1626 UBE1C AGAUGAUCCUGAACAUAUA NM_003968 1627 UBE1C CAGCUAAACUACAGGAGGU NM_003968 1628 UBE1C GAAGAUGGAUAAAUGGCAU NM_003968 1629 UBE1C GGCUGAAGUUGCUGCAGAA NM_003968 1630 UBE1C GGUAACCUCUAUUGAAGAA NM_003968 1631 UBE1C GGAACCAUGUAAAGAAGUU NM_003968 1632 UBE1C AGAACACUGUAUUGAGUAU NM_003968 1633 UBE1C GCUGGAACCAUGUAAAGAA NM_003968 1634 UBE1C GAGAUGAUCCUGAACAUAU NM_003968 1635 UBE1C GAAGAAAAGAAGGAGAAUA NM_003968 1636 UBE1C GAAGAACGAACAAGGCCAA NM_198195 1637 UBE1DC1 GGACAAACAUGGAUGGAAU NM_024818 1638 UBE1DC1 GGAAGCAGCAGGAGGAAUA NM_024818 1639 UBE1DC1 GCUUAUAAUUCCUGGAGAA NM_198329 1640 UBE1DC1 AAUAAGUAAUGGUGGGUUA NM_198329 1641 UBE1DC1 ACAAGAAGAGGAAGAGAUA NM_024818 1642 UBE1DC1 GGUUAUACAAGAAGAGGAA NM_198329 1643 UBE1DC1 AAGAAGAGGAAGAGAUAAU NM_198329 1644 UBE1DC1 UGGAAGACCUCAUGGCCAA NM_198329 1645 UBE1DC1 AGGAAAACCUGUUGAUCUA NM_024818 1646 UBE1DC1 GCUCGAAUGACAAUAAAUA NM_198329 1647 UBE1DC1 GAACUAGCCAAUAUGAAUA NM_024818 1648 UBE1DC1 GGGAAUUGUAAGCGACUAU NM_024818 1649 UBE1DC1 AAGUAAAGUUCAAGCAGCA NM_024818 1650 UBE1DC1 ACAAGAGGUUAUACAAGAA NM_198329 1651 UBE1L CUGCAAAGCUGGAGGAGCA NM_003335 1652 UBE1L AGGAAGAGCCACUGGAAGA NM_003335 1653 UBE1L AGGAAGUGCUGAAGGCAAU NM_003335 1654 UBE1L CAGCACGGGUUGAGGGUGA NM_003335 1655 UBE1L CUUCGAAGCUACUGGAUGA NM_003335 1656 UBE1L UGGAAGAGCCACUGGAUGA NM_003335 1657 UBE1L GGACAGAGGAAGAGCCACU NM_003335 1658 UBE1L CCACAGAACUGGCAAGACU NM_003335 1659 UBE1L CCCAAGACUGUGAGACAUA NM_003335 1660 UBE1L CAGGAAGUGCUGAAGGCAA NM_003335 1661 UBE1L GGGCCUGAACCCAGACUUA NM_003335 1662 UBE1L UAAUAAAGUGCUUGAGGAU NM_003335 1663 UBE1L UCUCGGGAAUUGAGGGAAU NM_003335 1664 UBE1L GACCCAAGACUGUGAGACA NM_003335 1665 UBE1L CAUCUUUGCUAGUAAUCUA NM_003335 1666 UBE1L UGUCAUAAGCAUGGAGUUU NM_003335 1667 UBE1L GGGCAGUGCUACAGUAUUC NM_003335 1668 UBE1L AGCAGAAGGAACUGAACAA NM_003335 1669 UBE1L GGGCUAUCACUGAAGUCAA NM_003335 1670 UBE1L UGAACAAAGCCCUGGAAGU NM_003335 1671 UBE1L CUAAUAAAGUGCUUGAGGA NM_003335 1672 UBE1L GCAGGUGUCUUGAGCCCUA NM_003335 1673 UBE1L GAAUUGAGGGAAUGGUUGA NM_003335 1674 UBE1L CCUGGAGAUUGGAGACACA NM_003335 1675 UBE1L GCGAAUUGUGGGCCAGAUU NM_003335 1676 UBE1L CUACAGUAUUCAUGCCACA NM_003335 1677 UBE1L AUGGAGACUUGGUGACUUU NM_003335 1678 UBE1L CCAUGUGGACUUUGUGGUA NM_003335 1679 UBE1L CACAGUAGGCACUCAAUAA NM_003335 1680 UBE2A AUGCCAAGUUUCAGAAUUA NM_003336 1681 UBE2A CUAAAGGAGUACAGCAAUU NM_003336 1682 UBE2A GGAAUAUGGCCUACAGAGA NM_003336 1683 UBE2A GCAGAGGAAUGGAAACAAU NM_003336 1684 UBE2A GAACAAACGGGAAUAUGAA NM_003336 1685 UBE2A GGAAGGGAGCAUAGCAUAU NM_003336 1686 UBE2A GCAAGAAGGAGAAAGUUGA NM_003336 1687 UBE2A GUUGAAGGACUCAGCUAAA NM_003336 1688 UBE2A CAGGAGAACAAACGGGAAU NM_003336 1689 UBE2A GAGCAGAGGAAUGGAAACA NM_003336 1690 UBE2A CUAUGCAGAUGGUAGUAUA NM_003336 1691 UBE2A GGGAGCAGAGGAAUGGAAA NM_003336 1692 UBE2A AAUAUGGCCUACAGAGAAU NM_003336 1693 UBE2A AAUGAUUGCUGAAGUGUUU NM_003336 1694 UBE2A ACAAGUAACCCAUGUAAAA NM_003336 1695 UBE2A GAAUAUGGCCUACAGAGAA NM_003336 1696 UBE2A CAGCAAUUGUAGUAACUGA NM_003336 1697 UBE2A GUGAAUGUGUUUGGAAUAU NM_003336 1698 UBE2A GCAUAUCUGUGGCAAACUA NM_003336 1699 UBE2A GGAUGGAACAUUUAAACUU NM_003336 1700 UBE2A GAGAAUAGAAACAAAUCCA NM_003336 1701 UBE2A AAUAAACCACCUACAGUUA NM_003336 1702 UBE2A AGAACAAACGGGAAUAUGA NM_003336 1703 UBE2A AGCUGUACCAGGAGAACAA NM_003336 1704 UBE2A ACUCAAUUGUCCAUCUUUA NM_003336 1705 UBE2A AGUUAUUGCUGCAUGCUUU NM_003336 1706 UBE2A GCACAAGUAACCCAUGUAA NM_003336 1707 UBE2A CAAGAAGGAGAAAGUUGAA NM_003336 1708 UBE2A UCACUGAAGAAUAUCCAAA NM_003336 1709 UBE2A GAUACUAAGAUCUCAGUCA NM_003336 1710 UBE2B GAACAAAGCUGGAAUGAUU NM_003337 1711 UBE2B AUACAUAACUUCAGUGCAA NM_003337 1712 UBE2B CAAACGAGAAUAUGAGAAA NM_003337 1713 UBE2B AGGCUGAGGUGGCAGAAUA NM_003337 1714 UBE2B GGAGGGAAAUCUUGGUGUA NM_003337 1715 UBE2B CAAGAGACUUUGUCACUUA NM_003337 1716 UBE2B GGAAAACAAACGAGAAUAU NM_003337 1717 UBE2B CAUCUUAGUUUACUGGAUA NM_003337 1718 UBE2B GGCAAAGGCGGGAGGAUCA NM_003337 1719 UBE2B GCUUGUGUAUCUUGAUUAA NM_003337 1720 UBE2B AGACAUAACUGGUUUGACU NM_003337 1721 UBE2B GGUAGCAUAUGUUUAGAUA NM_003337 1722 UBE2B AGUUAUAUUUGGACCAGAA NM_003337 1723 UBE2B GCACAGCUUUAUCAGGAAA NM_003337 1724 UBE2B GCAGUGGAAUGCAGUUAUA NM_003337 1725 UBE2B GUAUUUAGGCCAUUUGUUA NM_003337 1726 UBE2B CAGGAAAACAAACGAGAAU NM_003337 1727 UBE2B ACACAGAGAACACAAAUUU NM_003337 1728 UBE2B ACAACAUCAUGCAGUGGAA NM_003337 1729 UBE2B GCACAUAUUGGAGGGAAAU NM_003337 1730 UBE2B GUUUAGAUAUCCUUCAGAA NM_003337 1731 UBE2B UAUCCUAUGCCUUCAAAUA NM_003337 1732 UBE2B GAGGGAAAUCUUGGUGUAA NM_003337 1733 UBE2B GAGUAAUUCUAGACAUAAC NM_003337 1734 UBE2B GAGCUGUGAUUAUGCCAUU NM_003337 1735 UBE2B GCACUUGCCUGUAGUCUCA NM_003337 1736 UBE2B GGGAGACGGGAUAGUGUUU NM_003337 1737 UBE2B ACUAAGUUAUUGCUGCAUA NM_003337 1738 UBE2B ACAAACGAGAAUAUGAGAA NM_003337 1739 UBE2B AGCAAUACCCUGUCUUUAA NM_003337 1740 UBE2C GGUAUAAGCUCUCGCUAGA NM_007019 1741 UBE2C AAGAAGUACCUGCAAGAAA NM_007019 1742 UBE2C CGGUUGAGCCCUUGUAUAU NM_007019 1743 UBE2C CCACAGCUUUUAAGAAGUA NM_007019 1744 UBE2C CCAUGGAGCAGCUGGAACA NM_007019 1745 UBE2C GGAGAACCCAACAUUGAUA NM_007019 1746 UBE2C GUAUAGGACUCUUUAUCUU NM_007019 1747 UBE2C CUGGAACAGUAUAUGAAGA NM_007019 1748 UBE2C UGGAGCAGCUGGAACAGUA NM_007019 1749 UBE2C UAAAUUAAGCCUCGGUUGA NM_007019 1750 UBE2C AGAAGUACCUGCAAGAAAC NM_007019 1751 UBE2C UUAAGAAGUACCUGCAAGA NM_007019 1752 UBE2C UAUCUUGAGCUGUGGUAUU NM_007019 1753 UBE2C GUUGAGCCCUUGUAUAUUA NM_007019 1754 UBE2C UGCAAGAAACCUACUCAAA NM_007019 1755 UBE2C CAGACAACCUUUUCAAAUG NM_007019 1756 UBE2C UAGGAGAACCCAACAUUGA NM_007019 1757 UBE2C CAAGAAACCUACUCAAAGC NM_181799 1758 UBE2C CAGCUGGAACAGUAUAUGA NM_007019 1759 UBE2C GCAAGAAACCUACUCAAAG NM_007019 1760 UBE2C GAGCAGCUGGAACAGUAUA NM_007019 1761 UBE2C GAGCCCUUGUAUAUUAAAU NM_007019 1762 UBE2C CGAGCGAGUUCCUGUCUCU NM_007019 1763 UBE2C GGACCAUUCUGCUCUCCAU NM_007019 1764 UBE2C GGUCUGCCCUGUAUGAUGU NM_007019 1765 UBE2C UACAAUGCGCCCACAGUGA NM_007019 1766 UBE2C UCUAGGAGAACCCAACAUU NM_007019 1767 UBE2C UAACAUAUGCCUGGACAUC NM_007019 1768 UBE2C ACAAUGCGCCCACAGUGAA NM_007019 1769 UBE2C GGUUGAGCCCUUGUAUAUU NM_007019 1770 UBE2D1 GAGAAUGGACUCAGAAAUA NM_003338 1771 UBE2D1 CAACAGACAUGCAAGAGAA NM_003338 1772 UBE2D1 GCAUUGAGAAAGACAUUUA NM_003338 1773 UBE2D1 CAGAAAGAAUUGAGUGAUC NM_003338 1774 UBE2D1 GGAAGUAUUUGUCUCGAUA NM_003338 1775 UBE2D1 GAAAGAAUUGAGUGAUCUA NM_003338 1776 UBE2D1 UUGUAUGCAUUGAGAAAGA NM_003338 1777 UBE2D1 CCAUGAAACCAUUUGAUUU NM_003338 1778 UBE2D1 CAGCUGGACCUGUGGGAGA NM_003338 1779 UBE2D1 CAUAAACAGUAAUGGAAGU NM_003338 1780 UBE2D1 AGGAAGAUGUGUAACUUUU NM_003338 1781 UBE2D1 CUAAGUAGGAAGAUGUGUA NM_003338 1782 UBE2D1 UGAAUUAAUUGCACUGCUA NM_003338 1783 UBE2D1 AGGAUAUUCUGUAGAUUGA NM_003338 1784 UBE2D1 GUAGAUUGAUUGCAGAUUU NM_003338 1785 UBE2D1 CUGAAAAGCAACCAAAUUA NM_003338 1786 UBE2D1 AAGAGAAUGGACUCAGAAA NM_003338 1787 UBE2D1 GCAAGAGAAUGGACUCAGA NM_003338 1788 UBE2D1 GCACAAAUCUAUAAAUCAG NM_003338 1789 UBE2D1 CAUCCAAACAUAAACAGUA NM_003338 1790 UBE2D1 AGAGAAUGGACUCAGAAAU NM_003338 1791 UBE2D1 AGUACCAGAUAUUGCACAA NM_003338 1792 UBE2D1 CCAUGGCGCUGAAGAGGAU NM_003338 1793 UBE2D1 GGAAGAUGUGUAACUUUUA NM_003338 1794 UBE2D1 CAACAUUAGCAGUAAAUUG NM_003338 1795 UBE2D1 UGUCUAAGAUGUCAGUUUU NM_003338 1796 UBE2D1 CCCAACGGCUGAUAAUUAA NM_003338 1797 UBE2D1 GAUCUACAAUGCAGCUGAA NM_003338 1798 UBE2D1 GAAAUGAUCUUUACACUGU NM_003338 1799 UBE2D1 CAAUGCAGCUGAAAAGCAA NM_003338 1800 UBE2D2 UGGAUAACCUCUACAAAUA NM_003339 1801 UBE2D2 GGGAAUGGACUCAGAAGUA NM_003339 1802 UBE2D2 CAGCAUUUGUCUUGAUAUU NM_003339 1803 UBE2D2 GAGAAAAGUACAACAGAAU NM_003339 1804 UBE2D2 CUAUCAGGGUGGAGUAUUU NM_003339 1805 UBE2D2 CAACAGAAUAGCUCGGGAA NM_003339 1806 UBE2D2 AGAGAAUCCACAAGGAAUU NM_003339 1807 UBE2D2 CUACAAAACAGAUAGAGAA NM_003339 1808 UBE2D2 GAAGAGAAUCCACAAGGAA NM_003339 1809 UBE2D2 AGAGAAAAGUACAACAGAA NM_003339 1810 UBE2D2 AGAAGUAUGCGAUGUAAUU NM_003339 1811 UBE2D2 GGAUAACCUCUACAAAUAA NM_003339 1812 UBE2D2 AAGAGAAUCCACAAGGAAU NM_003339 1813 UBE2D2 CAAAACAGAUAGAGAAAAG NM_003339 1814 UBE2D2 GGAAUGGACUCAGAAGUAU NM_003339 1815 UBE2D2 CUACAAUAAUGGGGCCAAA NM_003339 1816 UBE2D2 GGAGAUGAUAUGUUCCAUU NM_003339 1817 UBE2D2 CAAAAGUACUCUUGUCCAU NM_003339 1818 UBE2D2 ACAAGGAAUUGAAUGAUCU NM_003339 1819 UBE2D2 UGAAGAGAAUCCACAAGGA NM_003339 1820 UBE2D2 UUGGAUAACCUCUACAAAU NM_003339 1821 UBE2D2 CAGAAUAGCUCGGGAAUGG NM_181838 1822 UBE2D2 GAAAAGUACAACAGAAUAG NM_003339 1823 UBE2D2 GCUCGGGAAUGGACUCAGA NM_003339 1824 UBE2D2 CAAUCCAGAUGAUCCUUUA NM_003339 1825 UBE2D2 GCAUUUGUCUUGAUAUUCU NM_003339 1826 UBE2D2 GAAGUAUGCGAUGUAAUUA NM_003339 1827 UBE2D2 CACAAGGAAUUGAAUGAUC NM_003339 1828 UBE2D2 CAGCACUAACUAUUUCAAA NM_003339 1829 UBE2D2 GGCAGCAUUUGUCUUGAUA NM_003339 1830 UBE2D3 UGGCAGAGCUGGUGUGAGA NM_003340 1831 UBE2D3 GCUCUAACAUGCUGAAGAA NM_003340 1832 UBE2D3 GAGCAUACACCGAGAGAGU NM_003340 1833 UBE2D3 GCUUGGAGCUAUUAGUUAA NM_003340 1834 UBE2D3 GGAAAUUGGAAGUCAAACA NM_003340 1835 UBE2D3 AGAGAUAAGUACAACAGAA NM_003340 1836 UBE2D3 GAGAUAAGUACAACAGAAU NM_003340 1837 UBE2D3 GCGCUGAAACGGAUUAAUA NM_003340 1838 UBE2D3 GAACAGAAAAUGUGAUGUA NM_003340 1839 UBE2D3 GCAUACACCGAGAGAGUGA NM_003340 1840 UBE2D3 GUGAGGAGCCAGACGACAA NM_003340 1841 UBE2D3 AAAUGGAGCAUGUGUAUUA NM_003340 1842 UBE2D3 CCGGGAUAAUCAAGAGUUU NM_003340 1843 UBE2D3 CUGAAUAAAUGAUGCAAGU NM_003340 1844 UBE2D3 CAACAGAAUAUCUCGGGAA NM_181887 1845 UBE2D3 GAUGAGUGAUCAACUAAUA NM_003340 1846 UBE2D3 GAUUUGAGGUUACAUGAUA NM_003340 1847 UBE2D3 CAGCAUUUGUCUCGAUAUU NM_003340 1848 UBE2D3 GAGAAUGGAAAUUGGAAGU NM_003340 1849 UBE2D3 AUCAAAGGAUACAGCAUUA NM_003340 1850 UBE2D3 GAAACGGAUUAAUAAGGAA NM_003340 1851 UBE2D3 GCAAGUUGUCAAUGGAUGA NM_003340 1852 UBE2D3 UGUUAGAGAUUUGAGGUUA NM_003340 1853 UBE2D3 CAGACAGAGAUAAGUACAA NM_181886 1854 UBE2D3 AAACAGACAGAGAUAAGUA NM_003340 1855 UBE2D3 GGUUACAUGAUAUGCUUUA NM_003340 1856 UBE2D3 CAUCAAAGGAUACAGCAUU NM_003340 1857 UBE2D3 CUAACAUGCUGAAGAAAUC NM_003340 1858 UBE2D3 UGAUAUGUUUCAUUGGCAA NM_181888 1859 UBE2E1 CCAAGAAGAAGGAGAGUAA NM_003341 1860 UBE2E1 GAGCAAACCGAGAAAGAAA NM_182666 1861 UBE2E1 GUGAAAACCUGUAGUGAAA NM_003341 1862 UBE2E1 GAGCAGAACAUGACAGAAU NM_182666 1863 UBE2E1 GGUUCUAUGUUGUGGACUA NM_003341 1864 UBE2E1 UGUCAUUAGUUCUGCAAUA NM_003341 1865 UBE2E1 CGGAGGAGCCAGACACAAA NM_003341 1866 UBE2E1 AGAGAUGAGUAGUGCGUUU NM_003341 1867 UBE2E1 GGUAAAGAGUAGGGUAUUU NM_003341 1868 UBE2E1 GCUUGGACAUAUUGAAAGA NM_003341 1869 UBE2E1 AGAAGGAGCUGGCGGACAU NM_003341 1870 UBE2E1 GACAGUGGACCAAGAGAUA NM_003341 1871 UBE2E1 GGAAGGGAACAUUGAUAUU NM_003341 1872 UBE2E1 CCAUAUAAGAGAUGAGUAG NM_003341 1873 UBE2E1 GCUUGUAGUCUGUAAAUUU NM_003341 1874 UBE2E1 UGAAAUACCUUAAGCUGUU NM_003341 1875 UBE2E1 UGAAUCAGGACUUGUGAAA NM_003341 1876 UBE2E1 CCAAGAGAAUUCAGAAGGA NM_003341 1877 UBE2E1 GAGGGUGGGAGUUGGUAAA NM_003341 1878 UBE2E1 AAACCGAGAAAGAAACAAA NM_003341 1879 UBE2E1 GUAAAGUCAGCAUGAGCAA NM_003341 1880 UBE2E1 GAAAACCUGUAGUGAAAUA NM_003341 1881 UBE2E1 GAGAUACGCUACAUAAAUU NM_003341 1882 UBE2E1 GGGAGUUGGUAAAGAGUAG NM_003341 1883 UBE2E1 GAAGAGAGCUGCUUAUGAU NM_003341 1884 UBE2E1 GAGUAGGGUAUUUCUAUAA NM_003341 1885 UBE2E1 CAACCAGCAAACCGAGAAA NM_003341 1886 UBE2E1 GAGAGUAAAGUCAGCAUGA NM_003341 1887 UBE2E1 AAGAAGGAGAGUAAAGUCA NM_182666 1888 UBE2E1 CAAGAGAUACGCUACAUAA NM_182666 1889 UBE2E3 AAGAACAAGAGGAAAGAAA NM_006357 1890 UBE2E3 AUAUGAAGGUGGUGUGUUU NM_006357 1891 UBE2E3 GAGCAGAACACGACAGGAU NM_006357 1892 UBE2E3 ACCAAGAUGUCCAGUGAUA NM_006357 1893 UBE2E3 AGAAGGAGCUAGCUGAAAU NM_006357 1894 UBE2E3 GGUAAAUGCUAUCAAGAGU NM_006357 1895 UBE2E3 AGAGAUAACUUCACCAAGA NM_006357 1896 UBE2E3 CUGAAGAACAAGAGGAAAG NM_182678 1897 UBE2E3 AAGCAUAGCCACUCAGUAU NM_006357 1898 UBE2E3 ACACCAAACUCUCUAGCAA NM_006357 1899 UBE2E3 UGUAUUAAACCCAGAUCUA NM_006357 1900 UBE2E3 GCCUGAAGAACAAGAGGAA NM_182678 1901 UBE2E3 CAAGAGAUACGCAACAUAA NM_006357 1902 UBE2E3 CAAUAAACAUGCUCCUGAA NM_006357 1903 UBE2E3 GAAGGAGCUAGCUGAAAUA NM_006357 1904 UBE2E3 GCUAUCAAGAGUAGAACUU NM_006357 1905 UBE2E3 GGCAAAGGUCCGAUGAUGA NM_006357 1906 UBE2E3 GCAAAUCUUUAUAGCCUUU NM_006357 1907 UBE2E3 CCUAAAGGAGAUAACAUUU NM_006357 1908 UBE2E3 CUCCAGAGCCUGAAGAACA NM_006357 1909 UBE2E3 CCAAGAGAUACGCAACAUA NM_006357 1910 UBE2E3 GCCUAAAGGAGAUAACAUU NM_006357 1911 UBE2E3 UGAAAUAACCCUUGAUCCU NM_006357 1912 UBE2E3 GUAAAUGCUAUCAAGAGUA NM_006357 1913 UBE2E3 AGAACAAGAGGAAAGAAAA NM_182678 1914 UBE2E3 CACCAAACUCUCUAGCAAA NM_006357 1915 UBE2E3 GCAGUGUGAAGGAGCAGAA NM_006357 1916 UBE2E3 ACUCAGUAUUUGACCAACA NM_006357 1917 UBE2G1 GAGAAGUGGUUUAGGAAAA NM_003342 1918 UBE2G1 GGAUAGAACUUGAGACAGU NM_003342 1919 UBE2G1 GGAAGUAGUCUUUGGCUUA NM_003342 1920 UBE2G1 GGGAAGAUAAGUAUGGUUA NM_003342 1921 UBE2G1 ACAAAGAAAUUGCGAUGUA NM_003342 1922 UBE2G1 CUACUUAACUUCUGGGUUU NM_003342 1923 UBE2G1 GCACCCAAAUGUUGAUAAA NM_003342 1924 UBE2G1 GGAAGAUAGAAAUGGAGAA NM_003342 1925 UBE2G1 GGGUAAAUGCUUUGCUAUU NM_003342 1926 UBE2G1 GGUGUUUGAUUGUGAGAAU NM_003342 1927 UBE2G1 GAUUAAUGUUUGAGCUUCA NM_003342 1928 UBE2G1 GUAUAGAUCCCGUCACUAA NM_003342 1929 UBE2G1 CAAUAAAACAUGCCAGUUA NM_003342 1930 UBE2G1 GAGAAAUGCUUUGGCAGAA NM_003342 1931 UBE2G1 GUGGAAACCAUCAUGAUUA NM_003342 1932 UBE2G1 GAAGAUAGAAAUGGAGAAU NM_003342 1933 UBE2G1 GGAACUGGGCUGCAAUAAA NM_003342 1934 UBE2G1 GCAGAAGAGUGAAAGAACU NM_003342 1935 UBE2G1 UAAUGUUGAUGCUGCGAAA NM_003342 1936 UBE2G1 UCAUGUACAUCCACAAAUA NM_003342 1937 UBE2G1 GGGAAGAUAGAAAUGGAGA NM_003342 1938 UBE2G1 GUACAUAGCACAACAUGAU NM_003342 1939 UBE2G1 AGAGACUGCUUUUGAGUGA NM_003342 1940 UBE2G1 GCUAGUAACUUCACUUAUU NM_003342 1941 UBE2G1 GCACAACAUGAUCCGGAUA NM_003342 1942 UBE2G1 AUGCACAGCUACAGGCUUU NM_003342 1943 UBE2G1 GUUGAUUCCUUAUGCAAAU NM_003342 1944 UBE2G1 GCUACAGGCUUUCUACUUA NM_003342 1945 UBE2G1 AAUGGAGGGAAGAUAGAAA NM_003342 1946 UBE2G1 CCAGAGAAGUGGUUUAGGA NM_003342 1947 UBE2G2 ACAAAGGGCUUCAGGUAGA NM_003343 1948 UBE2G2 GAUCACAAGGUCAGGAAAU NM_003343 1949 UBE2G2 CCAUGAAUGAAGAGAACUU NM_003343 1950 UBE2G2 UCACAAAGGGCUUCAGGUA NM_003343 1951 UBE2G2 GAAAUGGGGUAAAUAGAAA NM_003343 1952 UBE2G2 GCUCUGUGCUGGUACCAAA NM_003343 1953 UBE2G2 UGACGAAAGUGGAGCUAAC NM_003343 1954 UBE2G2 UUACAAACCAUCACACUUA NM_003343 1955 UBE2G2 GGCCAAGGCAGGUAGAUCA NM_003343 1956 UBE2G2 UUACAGUAUUCCUCACAAA NM_003343 1957 UBE2G2 CCAAGCAGAUCGUCCAGAA NM_003343 1958 UBE2G2 GAGAUUUACCUGUGAGAUG NM_003343 1959 UBE2G2 GGCAGAUGCUUUUCUUAUA NM_003343 1960 UBE2G2 GGGAGCAGUUCUAUAAGAU NM_003343 1961 UBE2G2 GCAGAUGCUUUUCUUAUAA NM_003343 1962 UBE2G2 GCGAUGACCCCAUGGGCUA NM_182688 1963 UBE2G2 ACAGCUUACUGCAGUUUUA NM_003343 1964 UBE2G2 GUCAGGAAAUUGAGACCAU NM_003343 1965 UBE2G2 CAAGGCAGGUAGAUCACAA NM_003343 1966 UBE2G2 UGGCAGAGCCCAAUGACGA NM_182688 1967 UBE2G2 GCGAUGACCGGGAGCAGUU NM_003343 1968 UBE2G2 CCACUUGAUUACCCGUUAA NM_182688 1969 UBE2G2 GGCAACAGAGCGAGACUCA NM_003343 1970 UBE2G2 GAUCAUGGGCCCAGAAGAC NM_182688 1971 UBE2G2 GAGCAGUUCUAUAAGAUUG NM_003343 1972 UBE2G2 ACCAUCACACUUAGAAAUA NM_003343 1973 UBE2G2 CAACAGAGCGAGACUCAGU NM_003343 1974 UBE2G2 CAUCACACUUAGAAAUACU NM_003343 1975 UBE2G2 GGUUGUACCUGCCAGACUU NM_003343 1976 UBE2G2 GGAGCAGUUCUAUAAGAUU NM_182688 1977 UBE2H GGAAAUAGCCGCUCUGAUA NM_003344 1978 UBE2H AAGAGUACAUCCAGAAAUA NM_003344 1979 UBE2H GGACAGCACAGGAGGAGAA NM_003344 1980 UBE2H GAUAGGUAGAUGUGAGUAA NM_003344 1981 UBE2H CAGAAGAAUACAAGCAGAA NM_003344 1982 UBE2H GGGAGGACUUAAUGAAUUU NM_003344 1983 UBE2H CGGAGGAGGCGCUGAAAGA NM_003344 1984 UBE2H CAUGAGAAGCAGACUAUAA NM_003344 1985 UBE2H GGCAAGAGGCGGAUGGACA NM_003344 1986 UBE2H AAGAUGAGGCCCAGGAUAU NM_003344 1987 UBE2H ACUGAACUGUCGAAGGAAA NM_003344 1988 UBE2H UUAGAAAGGUUGCAGAUUU NM_003344 1989 UBE2H GGGAGCUAAUUAAGAGUAU NM_003344 1990 UBE2H UCAAGCUCAUCGAGAGUAA NM_003344 1991 UBE2H GUAUAAAGCAGGGAGCUAA NM_003344 1992 UBE2H AUAUGGAGUUGUAGUAGAA NM_003344 1993 UBE2H GCAGAAAAUUAAAGAGUAC NM_003344 1994 UBE2H CCAGAAGAAUACAAGCAGA NM_003344 1995 UBE2H GAAGAUGAGGCCCAGGAUA NM_003344 1996 UBE2H CCAAUAUAUUUGAGUCCUU NM_182697 1997 UBE2H CGCUGAAAGAACAGGAAGA NM_003344 1998 UBE2H GAUAUGGAGUUGUAGUAGA NM_003344 1999 UBE2H GAGAAGCAGACUAUAAUAU NM_003344 2000 UBE2H GAAGAAUACAAGCAGAAAA NM_182697 2001 UBE2H GAGAGUAAACAUGAGGUUA NM_003344 2002 UBE2H CUACUGAACUGUCGAAGGA NM_003344 2003 UBE2H GAGUGGACCUACCUGAUAA NM_182697 2004 UBE2H UGGGAGGACUUAAUGAAUU NM_182697 2005 UBE2H AGAAAUACGCCACGGAGGA NM_182697 2006 UBE2H AGUUAUUGGCCUAUCCUAA NM_003344 2007 UBE2I GAGGAAAGCAUGGAGGAAA NM_003345 2008 UBE21 GGGAAGGAGGCUUGUUUAA NM_003345 2009 UBE21 CCAUCUUAGAGGAGGACAA NM_194260 2010 UBE2I GAAAAGGGUCCGAGCACAA NM_003345 2011 UBE2I GAGCACAAGCCAAGAAGUU NM_003345 2012 UBE2I AGGAAAGCAUGGAGGAAAG NM_003345 2013 UBE2I GGAGGAACGUGUGGAGUUU NM_003345 2014 UBE2I AAUCUAAAGUUGCUCCAUA NM_003345 2015 UBE2I CAGCUCAAGCAGAGGCCUA NM_003345 2016 UBE2I GAAUACAGGAACUUCUAAA NM_003345 2017 UBE2I CAGAGUGGAGUACGAGAAA NM_003345 2018 UBE2I GCAGAGGCCUACACGAUUU NM_003345 2019 UBE2I GGGCCUGUGUCUUGGACUU NM_003345 2020 UBE2I ACAGGAACUUCUAAAUGAA NM_003345 2021 UBE2I GGAUCUGUGUUUGGUGAAA NM_003345 2022 UBE2I AGAGGAAAGCAUGGAGGAA NM_003345 2023 UBE2I CUGUGUUGCUGUUUAGGUA NM_003345 2024 UBE2I GAGGAAAGACCACCCAUUU NM_003345 2025 UBE2I GGAAGGAGGCUUGUUUAAA NM_003345 2026 UBE2I UAAAGUUGCUCCAUACAAU NM_003345 2027 UBE2I AGAAGGAAGGGAUUGGUUU NM_003345 2028 UBE2I GGGAUUGGUUUGGCAAGAA NM_003345 2029 UBE2I UGGAGGAACGUGUGGAGUU NM_003345 2030 UBE2I ACAGAGUGGAGUACGAGAA NM_194259 2031 UBE2I GCCAAAACAGAGUGGAGUA NM_194259 2032 UBE2I GCCCAGGAGAGGAAAGCAU NM_194259 2033 UBE2I GGAGGAAAGACCACCCAUU NM_194260 2034 UBE2I AAGCAGAGGCCUACACGAU NM_003345 2035 UBE2I GAGAGGAAAGCAUGGAGGA NM_194259 2036 UBE2I UAUCCAAGACCCAGCUCAA NM_194259 2037 UBE2J1 UGUAGAAUGUAUAGGGAUA NM_016021 2038 UBE2J1 GAGUAUAAGGACAGCAUUA NM_016336 2039 UBE2J1 AAGAAGAGCACUUGCCAAA NM_016336 2040 UBE2J1 GCAAAUAAGCUUUAAGGCA NM_016021 2041 UBE2J1 GCUUUAAGGCAGAAGUCAA NM_016021 2042 UBE2J1 CAGCCUUCGUGGAGUAUAA NM_016021 2043 UBE2J1 UGAAAGAAGCGGCAGAAUU NM_016021 2044 UBE2J1 CCAAAGAACUGGCUAGGCA NM_016021 2045 UBE2J1 GAAUAUAUCUGGCAAACGA NM_016021 2046 UBE2J1 GAGAAUUACUAGUUACUCA NM_016336 2047 UBE2J1 GGGUAUAAUCUAAGAAUUG NM_016336 2048 UBE2J1 GUAUAGGGAUAGAAGAGUU NM_016021 2049 UBE2J1 CGACGAAUAUAUCUGGCAA NM_016021 2050 UBE2J1 AAAUAAGCUUUAAGGCAGA NM_016021 2051 UBE2J1 UAGGAGAUGUACUGGAAUU NM_016021 2052 UBE2J1 CUAUAUUGCCCUUUGAAAU NM_016336 2053 UBE2J1 CAGAGAAGGUUGUCUACUU NM_016021 2054 UBE2J1 CAGCAGAGUCAGAGAAGGU NM_016021 2055 UBE2J1 CAUAGGAGAUGUACUGGAA NM_016021 2056 UBE2J1 CCUAAACAUUCUUCAGUGA NM_016021 2057 UBE2J1 AAGCAAAACUCCUCAAGUA NM_016021 2058 UBE2J1 GUCAAACAUUUAUGAGGAA NM_016021 2059 UBE2J1 GAAUGGCACUUCACGGUUA NM_016336 2060 UBE2J1 AGUCAGAGAAGGUUGUCUA NM_016021 2061 UBE2J1 CCAUAGGUUCUCUAGAUUA NM_016021 2062 UBE2J1 GAAAGAAGCGGCAGAAUUG NM_016021 2063 UBE2J1 CAAAUAAGCUUUAAGGCAG NM_016021 2064 UBE2J1 GGCUAAUGGUCGAUUUGAA NM_016021 2065 UBE2J1 UGGCAGCCUUCGUGGAGUA NM_016021 2066 UBE2J1 GCUAAGAAUACCUCCAUGA NM_016021 2067 UBE2J2 ACAGAAAGCACAAGACGAA NM_058167 2068 UBE2J2 GCUCCUAGGUUUAGCUUUU NM_058167 2069 UBE2J2 UCAGUGAGUUGAAAGGAAA NM_058167 2070 UBE2J2 CUGAAGUCGUGGAGGAGAU NM_194457 2071 UBE2J2 GUUGAAAGGAAAUGUGUUU NM_058167 2072 UBE2J2 UAUUAGAUGUGGUCACUUA NM_058167 2073 UBE2J2 ACAAAUGUGUUUACAGUCA NM_058167 2074 UBE2J2 GUAUAGAGACGUCGGACUU NM_058167 2075 UBE2J2 CCACCAGGCUCCUAGGUUU NM_058167 2076 UBE2J2 GUGGAGGAGAUUAAACAAA NM_194458 2077 UBE2J2 GUGCUGGAUUUGUAGCUUA NM_058167 2078 UBE2J2 CGAACUUGUUUGUGAUAGU NM_194458 2079 UBE2J2 AAGUCGUGGAGGAGAUUAA NM_058167 2080 UBE2J2 CAGAGAAUUUCCUUUCAAA NM_194315 2081 UBE2J2 GUGCAGAGUUUAGCAUUUA NM_194457 2082 UBE2J2 AGUGCAGAGUUUAGCAUUU NM_058167 2083 UBE2J2 GGGUUUGGUCUCAGCAUUU NM_058167 2084 UBE2J2 ACGGGAGGUUUAAGUGCAA NM_194457 2085 UBE2J2 UGGAGGAGAUUAAACAAAA NM_194458 2086 UBE2J2 UGGCUAUUAUCAUGGAAAA NM_058167 2087 UBE2J2 CACCAGGCUCCUAGGUUUA NM_058167 2088 UBE2J2 UGAGCUUCAUGGUGGAGAA NM_058167 2089 UBE2J2 GCACAAGACGAACUCAGUA NM_058167 2090 UBE2J2 GGCCUUGUGUGCUGGAUUU NM_058167 2091 UBE2J2 GUGUUUACAGUCAGAAUGA NM_058167 2092 UBE2J2 UUAUGAAGGUGGCUAUUAU NM_058167 2093 UBE2J2 AGACGAACUCAGUAGCAGA NM_194315 2094 UBE2J2 GUGGCUAUUAUCAUGGAAA NM_194316 2095 UBE2J2 CCAGAGAAUUUCCUUUCAA NM_194315 2096 UBE2J2 CCCAGUAUCUAUAUGAUCA NM_194458 2097 UBE2L3 CCUCAGUUCUUGUGUGAAA NM_003347 2098 UBE2L3 UGAAGGAGCUUGAAGAAAU NM_003347 2099 UBE2L3 UAAGAAUGCUGAAGAGUUU NM_003347 2100 UBE2L3 GCUGAAGAGUUUACAAAGA NM_003347 2101 UBE2L3 CCGCAAAUGUGGGAUGAAA NM_003347 2102 UBE2L3 UGAUGAAUCUCGCCAGAAA NM_003347 2103 UBE2L3 ACAAAGAAAUAUGGGGAAA NM_003347 2104 UBE2L3 CUGAAGAGUUUACAAAGAA NM_003347 2105 UBE2L3 GAAAAGUGAUGAUGGAUUU NM_003347 2106 UBE2L3 CCAGAAUGUCCGUUUGAAA NM_003347 2107 UBE2L3 GUGGAGAAGAUGACUUAAA NM_003347 2108 UBE2L3 GAUGAAGGAGCUUGAAGAA NM_198157 2109 UBE2L3 GACUAGAUCCUGUGGAGAA NM_003347 2110 UBE2L3 CAGAGAAGCCCUAUAAUCA NM_003347 2111 UBE2L3 GCACAGAGAAGCCCUAUAA NM_003347 2112 UBE2L3 CCACCGAAGAUCACAUUUA NM_003347 2113 UBE2L3 GCAGAAAAGUGAUGAUGGA NM_003347 2114 UBE2L3 CCUCAUAGCACUGGUGAAU NM_003347 2115 UBE2L3 GUAAGAAUGCUGAAGAGUU NM_003347 2116 UBE2L3 UGACCUAGCUGAAGAAUAC NM_003347 2117 UBE2L3 CCUUCAGAAUCGAAAUCAA NM_003347 2118 UBE2L3 GAGAAGAUGACUUAAACUU NM_003347 2119 UBE2L3 GCAGGAGGCUGAUGAAGGA NM_003347 2120 UBE2L3 GCCAGUAAUUAGUGCCGAA NM_003347 2121 UBE2L3 GGGCUGACCUAGCUGAAGA NM_003347 2122 UBE2L3 ACCCAAACAUCGACGAAAA NM_003347 2123 UBE2L3 AAGCAGGACUCUGUGGAAA NM_003347 2124 UBE2L3 GCUUGAAGAAAUCCGCAAA NM_003347 2125 UBE2L3 CCAGGUUGAUGAAGCUAAU NM_003347 2126 UBE2L3 GGUUGAUGAAGCUAAUUUA NM_003347 2127 UBE2L6 GGACGAGAACGGACAGAUU NM_004223 2128 UBE2L6 GUGAAUAGACCGAAUAUCA NM_004223 2129 UBE2L6 UGAAGGAGCUGGAGGAUCU NM_004223 2130 UBE2L6 CCUCAGACUGUGAAGUAUA NM_004223 2131 UBE2L6 GAAAGAAUGCCGAAGAGUU NM_004223 2132 UBE2L6 AAACCAUGUUCUUGCUUAA NM_004223 2133 UBE2L6 GAGUUUAAGUUUGCAGUUA NM_004223 2134 UBE2L6 CUUCUUAGGUUGUUAGUCA NM_004223 2135 UBE2L6 GGUUGUUAGUCAUUAGUUU NM_004223 2136 UBE2L6 GCACUGGAUCCUCGGCAUA NM_004223 2137 UBE2L6 AGUGAGAACUGGAAGCCUU NM_004223 2138 UBE2L6 GAGUGUGUGUGUUGUGUAU NM_004223 2139 UBE2L6 GUCACAAUCUGAAGAAUCA NM_004223 2140 UBE2L6 AUCCGGAGCUGUUCAGAAA NM_004223 2141 UBE2L6 UGAUGGGAAUAUACAGAUU NM_004223 2142 UBE2L6 CCGGAGCUGUUCAGAAAGA NM_004223 2143 UBE2L6 GCUGGUGAAUAGACCGAAU NM_004223 2144 UBE2L6 GUUCAGAAAGAAUGCCGAA NM_004223 2145 UBE2L6 GUUUAAGUUUGCAGUUACA NM_004223 2146 UBE2L6 UCAGAAAGAAUGCCGAAGA NM_004223 2147 UBE2L6 CCAAGCCACUGAUGGGAAU NM_004223 2148 UBE2L6 AAAGAAUGCCGAAGAGUUC NM_004223 2149 UBE2L6 GGCCUCAGACUGUGAAGUA NM_004223 2150 UBE2L6 UGAUCAAAUUCACAACCAA NM_004223 2151 UBE2L6 GGACCAGGCCUCAGACUGU NM_004223 2152 UBE2L6 GAAACCAUGUUCUUGCUUA NM_004223 2153 UBE2L6 CAUCAUCAGCAGUGAGAAC NM_004223 2154 UBE2L6 GCAUGCGAGUGGUGAAGGA NM_004223 2155 UBE2L6 GGAGCUGUUCAGAAAGAAU NM_004223 2156 UBE2L6 GUAUAUAUCCUCCAGCAUU NM_004223 2157 UBE2M ACAUUGACCUCGAGGGCAA NM_003969 2158 UBE2M CAGAGGUCCUGCAGAACAA NM_003969 2159 UBE2M CCGAGGACCCACUGAACAA NM_003969 2160 UBE2M GGAAGUUUGUGUUCAGUUU NM_003969 2161 UBE2M AGGUGAAGUGUGAGACAAU NM_003969 2162 UBE2M CUACAAGAGUGGGAAGUUU NM_003969 2163 UBE2M GGAUCCAGAAGGACAUAAA NM_003969 2164 UBE2M GAAAUAGGGUUGGCGCAUA NM_003969 2165 UBE2M CUGCCCAAGACGUGUGAUA NM_003969 2166 UBE2M UUAAGGUGGGCCAGGGUUA NM_003969 2167 UBE2M AGAAGAAGGAGGAGGAGUC NM_003969 2168 UBE2M AGCCAGUCCUUACGAUAAA NM_003969 2169 UBE2M GAUGAGGGCUUCUACAAGA NM_003969 2170 UBE2M AGGACAUAAACGAGCUGAA NM_003969 2171 UBE2M CAAGGUGAAGUGUGAGACA NM_003969 2172 UBE2M CUGCGGAUCCAGAAGGACA NM_003969 2173 UBE2M AAGCCAGUCCUUACGAUAA NM_003969 2174 UBE2M GAAGCCAGUCCUUACGAUA NM_003969 2175 UBE2M GAGCUGAACCUGCCCAAGA NM_003969 2176 UBE2M CAGACGACCUCCUCAACUU NM_003969 2177 UBE2M GCACCAAGGGCAGCAGCAA NM_003969 2178 UBE2M GCCUCAACAUCCUCAGAGA NM_003969 2179 UBE2M UGAAGCAGCAGAAGAAGGA NM_003969 2180 UBE2M AAAUAGGGUUGGCGCAUAC NM_003969 2181 UBE2M GAUAUCAGCUUCUCAGAUC NM_003969 2182 UBE2M GCCCAAGACGUGUGAUAUC NM_003969 2183 UBE2M UAAUUUAUGGCCUGCAGUA NM_003969 2184 UBE2M GGACAUAAACGAGCUGAAC NM_003969 2185 UBE2M CCACGUGCCCCUAGUUAUU NM_003969 2186 UBE2M UUUAACACCAGGCUAACUA NM_003969 2187 UBE2N CAACGAAGCCCAAGCCAUA NM_003348 2188 UBE2N GGACACAGUCUUAGAAACA NM_003348 2189 UBE2N GGCUAUAUGCCAUGAAUAA NM_003348 2190 UBE2N AGACAAGUUGGGAAGAAUA NM_003348 2191 UBE2N GAAGGUAGUUGUCAGGUUA NM_003348 2192 UBE2N CAUCUGGAUUGUUGUGAAA NM_003348 2193 UBE2N CAUCCUGGUUUAAGUAUAA NM_003348 2194 UBE2N GGGAGGUAGUUUAAUUUUA NM_003348 2195 UBE2N CCGAACCAGAUGAGAGCAA NM_003348 2196 UBE2N CAGAUGAUCCAUUAGCAAA NM_003348 2197 UBE2N GGACUAGGCUAUAUGCCAU NM_003348 2198 UBE2N GUAGACAAGUUGGGAAGAA NM_003348 2199 UBE2N UAUAAAGCACUGUGAAUGA NM_003348 2200 UBE2N GCAUCAAAGCCGAACCAGA NM_003348 2201 UBE2N CAUCAAAGCCGAACCAGAU NM_003348 2202 UBE2N GGGAGGGACUUUUAAACUU NM_003348 2203 UBE2N GGGAAGAAUAUGUUUAGAU NM_003348 2204 UBE2N ACACAGUCUUAGAAACAUU NM_003348 2205 UBE2N UCUGGAAACUUCUGUAAAU NM_003348 2206 UBE2N CCAGAUGAUCCAUUAGCAA NM_003348 2207 UBE2N CUAAUAACAUUGCUGUCAA NM_003348 2208 UBE2N AGCCCAAGCCAUAGAAACA NM_003348 2209 UBE2N CAAAUGAUGUAGCGGAGCA NM_003348 2210 UBE2N CCAUCCUGGUUUAAGUAUA NM_003348 2211 UBE2N GAUCUAAUUGCAUUGGUUA NM_003348 2212 UBE2N GAGCAGAGGCUAGAAGUAU NM_003348 2213 UBE2N UAACCAGGUCUUUAGAAUA NM_003348 2214 UBE2N AUAGAAACAGCUAGAGCAU NM_003348 2215 UBE2N AGAUGAUCCAUUAGCAAAU NM_003348 2216 UBE2N AACCAGGUCUUUAGAAUAU NM_003348 2217 UBE2Q AUGAAGGAGCUCAGGGAUA NM_017582 2218 UBE2Q CAGAAGACUUAGAUCACUA NM_017582 2219 UBE2Q CCAUAGAGUCAGUGAUCAU NM_017582 2220 UBE2Q AUGAAAUGAAAGAGGAAGA NM_017582 2221 UBE2Q CUAUGAAAUGAAAGAGGAA NM_017582 2222 UBE2Q CCAGAUCCUCAAAGAGAAA NM_017582 2223 UBE2Q UGGAGAGGCUGGUGGACAU NM_017582 2224 UBE2Q CCUCAAAGAGAAAGAAGGA NM_017582 2225 UBE2Q AAGAUGAAGAUGAGGAGAU NM_017582 2226 UBE2Q GCUGGUGGACAUAAAGAAA NM_017582 2227 UBE2Q AGAUGAUGGCAUUGGAAAA NM_017582 2228 UBE2Q CUUAAAUGGUGCAGUGUCU NM_017582 2229 UBE2R2 GGAAAUGGAGAGACAGUAA NM_017811 2230 UBE2R2 CCACAACCCUGGCGGAAUA NM_017811 2231 UBE2R2 CAGUAAAGGAAAAGACAAA NM_017811 2232 UBE2R2 CGACAUUGAUGAUGAAGAU NM_017811 2233 UBE2R2 GGAGAGACAGUAAAGGAAA NM_017811 2234 UBE2R2 GGAUCGAAAGCCUGAAAUA NM_017811 2235 UBE2R2 GCAUAUACUGGGUAGCAAA NM_017811 2236 UBE2R2 GUGCUAAGCCUGAUGAAAU NM_017811 2237 UBE2R2 AGACAAAGAAUAUGCUGAA NM_017811 2238 UBE2R2 AGGAAGAUGCCGACUGUUA NM_017811 2239 UBE2R2 AAGAUGAGGAGGAGGAAGA NM_017811 2240 UBE2R2 CCACUAAGGCCGAAGCAGA NM_017811 2241 UBE2R2 GAGAGACAGUAAAGGAAAA NM_017811 2242 UBE2R2 GUUCACAAGUGCUGCAUAU NM_017811 2243 UBE2R2 UCAGUUAUGUUCAGGAAAU NM_017811 2244 UBE2R2 GACCUUUAAUGGAGAGAGA NM_017811 2245 UBE2R2 UCUGAAAGGUGGAAUCCUA NM_017811 2246 UBE2R2 AGGUUUAGCUGCUCAUUUA NM_017811 2247 UBE2R2 GAUCGAAAGCCUGAAAUAA NM_017811 2248 UBE2R2 CAUCAGGGACUUUGUGCUA NM_017811 2249 UBE2R2 GAGUAACCCUCCACAGAAU NM_017811 2250 UBE2R2 GCGGAAUACUGCAUCAAAA NM_017811 2251 UBE2R2 CCUUCAGAUUCUUGACCAA NM_017811 2252 UBE2R2 UUAUGAGAAUGGAGAUGUA NM_017811 2253 UBE2R2 AUCGAAAGCCUGAAAUAAA NM_017811 2254 UBE2R2 UCGAAAGCCUGAAAUAAAU NM_017811 2255 UBE2R2 ACAGAAUGUUCACAGCAAA NM_017811 2256 UBE2R2 GUGGAAUCCUACUCAGAAU NM_017811 2257 UBE2R2 CCAUGAAACCAUCGUAACA NM_017811 2258 UBE2R2 GCUGAAAUUAUUAGGAAAC NM_017811 2259 UBE2S UGGAGAACUACGAGGAGUA NM_014501 2260 UBE2S GCAUCAAGGUCUUUCCCAA NM_014501 2261 UBE2S CCAAGAAGCAUGCUGGCGA NM_014501 2262 UBE2S UCAACGUGCUCAAGAGGGA NM_014501 2263 UBE2V2 GGAAAUAGGUGUAUGGAUA NM_003350 2264 UBE2V2 GGACAAACAUACAACAAUU NM_003350 2265 UBE2V2 GAUGAAAGCGUGUGGAGAA NM_003350 2266 UBE2V2 CUAAUGAUGUCCAAAGAAA NM_003350 2267 UBE2V2 GGAAGAACUUGAAGAAGGA NM_003350 2268 UBE2V2 CAGAAUAUAUAGCCUGAAA NM_003350 2269 UBE2V2 CGAAAUAGAAUUCAGGUUU NM_003350 2270 UBE2V2 GUGUACUUCUUGUGAAUUA NM_003350 2271 UBE2V2 AGUAGAAUGUGGACCUAAA NM_003350 2272 UBE2V2 AGUUGUACUUCAAGAGCUA NM_003350 2273 UBE2V2 CCUCAGAGACUGUGCCAUU NM_003350 2274 UBE2V2 GAGUUAAAGUUCCUCGUAA NM_003350 2275 UBE2V2 AAAGAGAGCUGCAGUUGAA NM_003350 2276 UBE2V2 AGUUAAAGUUCCUCGUAAU NM_003350 2277 UBE2V2 GUUCAGGAUUGUUUUGAUA NM_003350 2278 UBE2V2 GCACUGUCAUUUAAACAUA NM_003350 2279 UBE2V2 AGGCAUGAUUAUUGGGCCA NM_003350 2280 UBE2V2 GAAAUAGGUGUAUGGAUAU NM_003350 2281 UBE2V2 GUUGGAAGAACUUGAAGAA NM_003350 2282 UBE2V2 GAUGAAGAUAUGACACUUA NM_003350 2283 UBE2V2 AUAAAUAAUUCCAGUGGGA NM_003350 2284 UBE2V2 CCAAGGACAAAUUAUGAAA NM_003350 2285 UBE2V2 GCAUACCAGUGUUAGCAAA NM_003350 2286 UBE2V2 AAGCUGUUCUUGUGUGUUA NM_003350 2287 UBE2V2 CUGGACAUUUGUAAGAAUA NM_003350 2288 UBE2V2 AGAACUUGAAGAAGGACAA NM_003350 2289 UBE2V2 ACAGAAAUGGCAUGCUUUA NM_003350 2290 UBE2V2 CUUACAAGGUGGACAGGCA NM_003350 2291 UBE2V2 AAGCAUGUGUGUUUCUAAA NM_003350 2292 UBE2V2 AGUGGAAGCAUGUGUGUUU NM_003350 2293 UBE3A AGACAAAGAUGAAGAUGAA NM_000462 2294 UBE3A GUAGAGAAAGAGAGGAUUA NM_130838 2295 UBE3A CCUCAGAACUUUAGUAACA NM_130838 2296 UBE3A UAACAGAAGAGAAGGUAUA NM_130839 2297 UBE3A AAGUAGAAACAGAGAACAA NM_000462 2298 UBE3A GGAAUUUGAAGGAGAACAA NM_130839 2299 UBE3A GGGAGAAAUUGGAAUGUUU NM_130839 2300 UBE3A GUAAUUAAAGUGAGGAGAA NM_000462 2301 UBE3A GGAGAAGAAAGAAGAAACA NM_000462 2302 UBE3A CAACAAAGUUAGGAAGUUU NM_000462 2303 UBE3A CAAAUGAAAUGGUAGUCAA NM_000462 2304 UBE3A CAAGAAAGGCGCUAGAAUU NM_130839 2305 UBE3A AGCAAAAGAUGAAGACAAA NM_000462 2306 UBE3A AGGCAUUGGUACAGAGCUU NM_000462 2307 UBE3A GCACCAGUGUUAUUGGAAA NM_000462 2308 UBE3A GGAAGAAGACUCAGAAGCA NM_130838 2309 UBE3A GAAGAGAAGGUAUAUGAAA NM_130839 2310 UBE3A GUUCAAGGCUUUUCGGAGA NM_130839 2311 UBE3A UCAGAAGUUUGGCGAAAUA NM_130839 2312 UBE3A CAGUCGAAAUCUAGUGAAU NM_000462 2313 UBE3A GCGUGAAAGUGUUACAUAU NM_000462 2314 UBE3A UGAAUGAGGUUCUAGAAAU NM_000462 2315 UBE3A GAGAUGAUCGCUAUGGAAA NM_000462 2316 UBE3A AGAUGAAGACAAAGAUGAA NM_000462 2317 UBE3A GAAGAAAGAAGAAACAAGA NM_130838 2318 UBE3A GGUGAUUGAUUGAUUGAUU NM_130838 2319 UBE3A AUUAGGGAGUUCUGGGAAA NM_130839 2320 UBE3A CAAUGAAGAAGAUGAUGAA NM_000462 2321 UBE3A AAGCAAAAGAUGAAGACAA NM_000462 2322 UBE3A GCUCACAGGGAGACAACAA NM_130839 2323 UBE3B AAGAAAGGCUUGUGCAGAA NM_130466 2324 UBE3B GUGCAAAUAUAAUGGGACA NM_183415 2325 UBE3B GGAGAGAGAUUGAUGACUU NM_130466 2326 UBE3B CCACAGUCCUUCAGAGUUU NM_130466 2327 UBE3B CAAAGAGGAUAAUGAGAGA NM_130466 2328 UBE3B AGAGAUAUCAGGAGAGAGA NM_130466 2329 UBE38 GCACAGGGCUGCAGAAAAU NM_130466 2330 UBE3B GGAACAAACACUAACCUAA NM_130466 2331 UBE3B CCUACAUCCAUGAGAAUUA NM_130466 2332 UBE3B CAGAUGGGUUCGUGAGUUU NM_130466 2333 UBE3B GGAAACAUGGCAAGGAAUU NM_130466 2334 UBE3B UCAGAAUCAAAGAGGAUAA NM_130466 2335 UBE3B UGGAAGAGCUGGUCACUAU NM_130466 2336 UBE3B GGGAGAGAGUGAUUUAUAA NM_130466 2337 UBE3B GGAUGGAAUUGUAGAGAAC NM_183414 2338 UBE3B GGGAUGGAAUUGUAGAGAA NM_130466 2339 UBE3B GCAGAGAGAUAUCAGGAGA NM_183414 2340 UBE38 UGUUAGAGGAGGAGACAGA NM_183415 2341 UBE3B GCAGAAGUCCAGAAGGUUU NM_130466 2342 UBE3B AGAUAUCAGGAGAGAGAUU NM_183414 2343 UBE3B CCGUCAGGCACGAGAAGAA NM_183414 2344 UBE3B GGGAAAAGGUGAAAGUCUU NM_183414 2345 UBE3B GAAUCAAAGAGGAUAAUGA NM_183414 2346 UBE3B CAACAGAUCAAGAACAUUU NM_130466 2347 UBE3B CCAGAGUGUUAGAGGAGGA NM_130466 2348 UBE3B GUGUGAAGUUUGUCAAUGA NM_130466 2349 UBE3B CAACAUGCCAGGUGACAUU NM_130466 2350 UBE3B UCAAGAACAUUUUGUGGUA NM_183414 2351 UBE3B CAGCAUGGGUUGAGUGUAC NM_130466 2352 UBE3B CAGAAGAAGUCCAACCUGA NM_183414 2353 UBE4A GGAGAAAACUGGAGGAAAA NM_004788 2354 UBE4A UGACAGACCAGGAGAAUAA NM_004788 2355 UBE4A GGAAAUGAACCUAGAAACA NM_004788 2356 UBE4A AGAAAUGGCAGUAGAGCUA NM_004788 2357 UBE4A GAAUAGAUACUGUGAACUA NM_004788 2358 UBE4A CAGUAGAGCUAGAAGAUCA NM_004788 2359 UBE4A CAUUAAUGCUGCUGAAUAU NM_004788 2360 UBE4A GCAACUUGGCAGAGAGAAU NM_004788 2361 UBE4A CAGAGUAACUUCACAUAAA NM_004788 2362 UBE4A GCAGGAAAUAUGUGAGCAA NM_004788 2363 UBE4A GCAUAGAAAGAAUGAAGAA NM_004788 2364 UBE4A GGAGCAACUUGAAUAGAUA NM_004788 2365 UBE4A GAGCAGACUUUCUAACAUA NM_004788 2366 UBE4A GAUAAUAGCGUGUCAGAGA NM_004788 2367 UBE4A UGAGAAGGAUCGAGGUGAA NM_004788 2368 UBE4A GGAAUAUGAUUAUGGCUUU NM_004788 2369 UBE4A GGGAGAGCAUUAAGGAUUU NM_004788 2370 UBE4A CGGGAGAGCAUUAAGGAUU NM_004788 2371 UBE4A AUAAAUAAGCCUGGGAAUA NM_004788 2372 UBE4A GGGCAAAUGUACCAGAAGA NM_004788 2373 UBE4A CCAAGAGGCUAAUACUAAA NM_004788 2374 UBE4A GAGGAUACCUUAAAGUGAA NM_004788 2375 UBE4A GCAUUAAGGAUUUGGCUGA NM_004788 2376 UBE4A GGAGUUGAAUGAUGAAGAA NM_004788 2377 UBE4A UCAAAGUACAGGAGGCCAA NM_004788 2378 UBE4A ACAACAACAUCUCAAGUAA NM_004788 2379 UBE4A AGUCAUGAUUCCAGUGUUU NM_004788 2380 UBE4A GGCCAAACACAGAACUAAA NM_004788 2381 UBE4A UAACUUACCAAGAGGCUAA NM_004788 2382 UBE4A UGUGUAGACUUCUGAAUAA NM_004788 2383 UBE4B AGGAAGAGAUGAAGAACAA NM_006048 2384 UBE4B CAAUAGAACUGUAGAAGAU NM_006048 2385 UBE4B CCGAGAAAGUGGAGGAGAU NM_006048 2386 UBE4B ACAGAAAUCUCUUGCUAAA NM_006048 2387 UBE4B GAAAAUGAUCGAAGAGAAA NM_006048 2388 UBE4B AGACAGAUAUGCUGAACUA NM_006048 2389 UBE4B CAAAGAAGCUGUUGGACCA NM_006048 2390 UBE4B UUGAAAACCCUGAGAAAUA NM_006048 2391 UBE4B AGAAGAUGUUGCAGAAUUU NM_006048 2392 UBE4B CGAUGGAAGAUGUGAAUGA NM_006048 2393 UBE4B CGGCAGACGCUGACAGAGA NM_006048 2394 UBE4B GAAAGGACAUGGAUGAGAA NM_006048 2395 UBE4B GGAGCAAGUAAUUGGGAUU NM_006048 2396 UBE4B GAGUUGGAAUAGAGGAAAA NM_006048 2397 UBE4B GCAACUAGACACCGCGAAA NM_006048 2398 UBE4B GGAGAUGAGGGUUGGGUUU NM_006048 2399 UBE4B UGUAGAAGAUGUUGCAGAA NM_006048 2400 UBE4B CGAGAAAGUGGAGGAGAUA NM_006048 2401 UBE4B UAAUGAAAGCCAAUGGAAA NM_006048 2402 UBE4B UGACACACGUUCAGAAGAA NM_006048 2403 UBE4B GGACAGACCUCUCAGCCAA NM_006048 2404 UBE4B CCGAGUUGGAAUAGAGGAA NM_006048 2405 UBE4B UGGAGGAGAUAGUGGCCAA NM_006048 2406 UBE4B AAGCGGAGCCUCAGUGAUA NM_006048 2407 UBE4B CUGCAAUGCUGAACUUUAA NM_006048 2408 UBE4B GAACUUUAAUCUUCAGCAA NM_006048 2409 UBE4B UGAAAAUGAUCGAAGAGAA NM_006048 2410 UBE4B UUGAAAUGAUUGAGAACCA NM_006048 2411 UBE4B GCUCAAUAGAACUGUAGAA NM_006048 2412 UBE4B ACAUGGAGGUUGAUGAAAA NM_006048 2413 UBL3 GAGAGUAAUUGUUGUGUAA NM_007106 2414 UBL3 AGACAUUACCAGAGCCAAA NM_007106 2415 UBL3 GAAAUAAACUGGUUCACUA NM_007106 2416 UBL3 UGAGAAGACUGGAGAGAGU NM_007106 2417 UBL3 CCAAAUAUUCUACGACUUA NM_007106 2418 UBL3 GUACAUAAAGCCUGAAUGA NM_007106 2419 UBL3 GGUCAGAGGAAUCGUGAGA NM_007106 2420 UBL3 GCACAGAAUACUAAACUGA NM_007106 2421 UBL3 GCACAGCACUAAAGCAUGA NM_007106 2422 UBL3 UCACAACAAUGGAUAGAAU NM_007106 2423 UBL3 GCAUAGAUCCAGUAAUGUA NM_007106 2424 UBL3 GUAUAUGACAAUUGGCCAA NM_007106 2425 UBL3 GUAAAUAGCACUAAACGUU NM_007106 2426 UBL3 GUUAAUUUGUGGACAGUCA NM_007106 2427 UBL3 GAGCAGAGUUUUAAAAUGA NM_007106 2428 UBL3 CAUAAAGCCUGAAUGAUGA NM_007106 2429 UBL3 GAUAUUAGUGCUUGCAAUU NM_007106 2430 UBL3 AAACAACAGUGAUGCAUUU NM_007106 2431 UBL3 GAAAGAAUUACGUCGCUUA NM_007106 2432 UBL3 GUAACUGAGUGUUUGUUUA NM_007106 2433 UBL3 AGAAGACUGGAGAGAGUAA NM_007106 2434 UBL3 GGUCAGCAGUCCAAAUAUU NM_007106 2435 UBL3 CAGCGUUGUUUAAAUGUAA NM_007106 2436 UBL3 GUAAACACAUGGAACUGAA NM_007106 2437 UBL3 UGUCACAUUAGGAGCAUUA NM_007106 2438 UBL3 GGUGAGAGCUGCAUAGAUC NM_007106 2439 UBL3 CAAAGCAUGUAUAUGACAA NM_007106 2440 UBL3 CGACAUUGCUUCAGAAACC NM_007106 2441 UBL3 GAGUAAUUGUUGUGUAAUC NM_007106 2442 UBL3 UGUGUGGUAUCUAGAAAUA NM_007106 2443 UBL4 GGAAACGACUCUCGGAUUA NM_014235 2444 UBL4 AGACAAUGGAGAAGGGCUU NM_014235 2445 UBL4 CUGAAGUGACUGAGACAAU NM_014235 2446 UBL4 GAACAGCUACAGAGGGAUU NM_014235 2447 UBL4 UGGAACAGCUACAGAGGGA NM_014235 2448 UBL4 UGACUGAGACAAUGGAGAA NM_014235 2449 UBL4 GGCCCUGGCAGAUGGGAAA NM_014235 2450 UBL4 GGGAAACGACUCUCGGAUU NM_014235 2451 UBL4 CUACAGAGGGAUUACGAGA NM_014235 2452 UBL4 GAAGGUGCUACUAGAAGAA NM_014235 2453 UBL4 AGAAGGUGCUACUAGAAGA NM_014235 2454 UBL4 AGCUCAACCUAGUGGUCAA NM_014235 2455 UBL4 GGAGAAGGUGCUACUAGAA NM_014235 2456 UBL4 UAGAAGAAGGCGAGGCCCA NM_014235 2457 UBL4 UGGAGAAGGUGCUACUAGA NM_014235 2458 UBL4 CAGCUGAUCUCCAAAGUCU NM_014235 2459 UBL4 ACUCCAAGCUCAACCUAGU NM_014235 2460 UBL4 GAAACGACUCUCGGAUUAU NM_014235 2461 UBL4 GCAGAUGGGAAACGACUCU NM_014235 2462 UBL4 GAGAAGGUGCUACUAGAAG NM_014235 2463 UBL4 AAACGACUCUCGGAUUAUA NM_014235 2464 UBL4 UCUGGCAGCUGAUCUCCAA NM_014235 2465 UBL4 UGAAGUGACUGAGACAAUG NM_014235 2466 UBL4 GCUGAUCUCCAAAGUCUUG NM_014235 2467 UBL4 GGCAGCUGAUCUCCAAAGU NM_014235 2468 UBL4 GAAGUGACUGAGACAAUGG NM_014235 2469 UBL4 CAACUCCAAGCUCAACCUA NM_014235 2470 UBL5 GGAUGAACCUGGAGCUUUA NM_024292 2471 UBL5 GGGAAGAAGGUCCGCGUUA NM_024292 2472 UBL5 GAUAGAUGCUUGUUUGUAA NM_024292 2473 UBL5 GAAGAAGGUCCGCGUUAAA NM_024292 2474 UBL5 GGAAGAAGGUCCGCGUUAA NM_024292 2475 UBL5 CUGAAGAAGUGGUACACGA NM_024292 2476 UBL5 AAGAAGUGGUACACGAUUU NM_024292 2477 UBL5 UGAUCGAGGUUGUUUGCAA NM_024292 2478 UBL5 CUAGGAUGAUCGAGGUUGU NM_024292 2479 UBL5 GGGAUGAACCUGGAGCUUU NM_024292 2480 UBL5 GCAACACGGAUGAUACCAU NM_024292 2481 UBL5 UGAAGAAGUGGUACACGAU NM_024292 2482 UBL5 GAACCUGGAGCUUUAUUAU NM_024292 2483 UBL5 UUAAAUGCAACACGGAUGA NM_024292 2484 UBL5 CCUGGAGCUUUAUUAUCAA NM_024292 2485 UBL5 GAAGAAGUGGUACACGAUU NM_024292 2486 UBL5 GGUACCCGUUGGAACAAGA NM_024292 2487 UBL5 GGAUAGAUGCUUGUUUGUA NM_024292 2488 UBL5 AAGAUUGUCCUGAAGAAGU NM_024292 2489 UBL5 ACCUGGAGCUUUAUUAUCA NM_024292 2490 UBL5 AAAUGCAACACGGAUGAUA NM_024292 2491 UBL5 UGGGAUAGAUGCUUGUUUG NM_024292 2492 UBL5 AGAUUGUCCUGAAGAAGUG NM_024292 2493 UBL5 UGAACCUGGAGCUUUAUUA NM_024292 2494 UBL5 GACCUUAAGAAGCUGAUUG NM_024292 2495 UBL5 AGAAGGUCCGCGUUAAAUG NM_024292 2496 UBL5 AAGAAGGUCCGCGUUAAAU NM_024292 2497 UBL5 GAAGGUCCGCGUUAAAUGC NM_024292 2498 UBL5 GAUGAUCGAGGUUGUUUGC NM_024292 2499 UBR1 GGAUGAAUAUGGAGAAACA NM_174916 2500 UBR1 UCAAAUAGCAUCAAGGAAA NM_174916 2501 UBR1 GAUUAUGGCUCAUCAGAAA NM_174916 2502 UBR1 GUGAAGCGAUUAAGAGAAA NM_174916 2503 UBR1 CUGCAGAUGAUGAGCGAAA NM_174916 2504 UBR1 GGACAAAUUGGGAAGAGUA NM_174916 2505 UBR1 GGACAGAAAGAUUAAGAAU NM_174916 2506 UBR1 AGAAAUGACUAUAUGGGAA NM_174916 2507 UBR1 CUUGGAAAGUGGAGAAUAU NM_174916 2508 UBR1 GAACAUAUGCAGAAGAAAA NM_174916 2509 UBR1 AAGAAGAACAGGAGGUGAA NM_174916 2510 UBR1 CCAGAAAUCUACUGCCUUA NM_174916 2511 UBR1 GCUUAGAGAAUGUCAUAAA NM_174916 2512 UBR1 GGGAAGAGUAUAUGCAGUA NM_174916 2513 UBR1 GGUCCUGGUUGAAGGUAAA NM_174916 2514 UBR1 CAAAUAGCAUCAAGGAAAU NM_174916 2515 UBR1 CUAUGGAAUUUGUGAAGUA NM_174916 2516 UBR1 GGAGAAAACAAGAAAACAA NM_174916 2517 UBR1 UAGAGGUACUAGUGGAAUA NM_174916 2518 UBR1 ACAAAGUCCUACAGAGUAU NM_174916 2519 UBR1 AGGAAGAUAUAAAGAGUCA NM_174916 2520 UBR1 AUAAACAACUGCAGAAAGA NM_174916 2521 UBR1 GCUGAGAUGUGGCGAAGAA NM_174916 2522 UBR1 CCAAAGAAGAGGUCACAAU NM_174916 2523 UBR1 CCAAAUGGCUUUUCAUAUU NM_174916 2524 UBR1 CUAUAUGGGAAGAGGAAAA NM_174916 2525 UBR1 UUUCAAAAGUGGAGAGACA NM_174916 2526 UBR1 CAAUAUGGACAGAAAGAUU NM_174916 2527 UBR1 GGUACUGAGAGGAUGGAAA NM_174916 2528 UBR1 CCGAAGACAGGUUGGGCAA NM_174916 2529 UCHL1 GGCCAAUAAUCAAGACAAA NM_004181 2530 UCHL1 CAUGAGAACUUCAGGAAAA NM_004181 2531 UCHL1 UUGAAGAGCUGAAGGGACA NM_004181 2532 UCHL1 GGGUAGAUGACAAGGUGAA NM_004181 2533 UCHL1 CCGCGAAGAUGCAGCUCAA NM_004181 2534 UCHL1 GCCAAGGUCUGCAGAGAAU NM_004181 2535 UCHL1 GAAGCAGACCAUUGGGAAU NM_004181 2536 UCHL1 GCAUGAGAACUUCAGGAAA NM_004181 2537 UCHL1 AGACCUUGGAUGUGGUUUA NM_004181 2538 UCHL1 GCUGAAGGGACAAGAAGUU NM_004181 2539 UCHL1 CUAUGAACUUGAUGGACGA NM_004181 2540 UCHL1 CUAAAAUGCUUCAGUACUU NM_004181 2541 UCHL1 GGAUGUGGUUUAAUUGUUU NM_004181 2542 UCHL1 CCAAUAAUCAAGACAAACU NM_004181 2543 UCHL1 CGGCCCAGCAUGAGAACUU NM_004181 2544 UCHL1 UAGAUGACAAGGUGAAUUU NM_004181 2545 UCHL1 CCCUGAAGACAGAGCAAAA NM_004181 2546 UCHL1 CAGCUCAAGCCGAUGGAGA NM_004181 2547 UCHL1 CCGAGAUGCUGAACAAAGU NM_004181 2548 UCHL1 GGGAUUUGAGGAUGGAUCA NM_004181 2549 UCHL1 GGUUUCUGUCUGUAAGUUA NM_004181 2550 UCHL1 GUUUCUGUCUGUAAGUUAA NM_004181 2551 UCHL1 CCUUGGAUGUGGUUUAAUU NM_004181 2552 UCHL1 GGAGGGACUUUGCUGAUUU NM_004181 2553 UCHL1 AAGCAGACCAUUGGGAAUU NM_004181 2554 UCHL1 ACGCAGUGGCCAAUAAUCA NM_004181 2555 UCHL1 UUAACAACGUGGAUGGCCA NM_004181 2556 UCHL1 CAGAGGACACCCUGCUGAA NM_004181 2557 UCHL1 CUGAAGGGACAAGAAGUUA NM_004181 2558 UCHL1 GGUGUGAGCUUCAGAUGGU NM_004181 2559 UCHL3 CAGCAUAGCUUGUCAAUAA NM_006002 2560 UCHL3 GAACAGAAGAGGAAGAAAA NM_006002 2561 UCHL3 CAGCAAUGCCUGUGGAACA NM_006002 2562 UCHL3 UGGUGAAACUAGUGAUGAA NM_006002 2563 UCHL3 GGCAAUUCGUUGAUGUAUA NM_006002 2564 UCHL3 AUUCAGAACAGAAGAGGAA NM_006002 2565 UCHL3 CUGAAGAACGAGCCAGAUA NM_006002 2566 UCHL3 CCUGAUGAACUAAGAUUUA NM_006002 2567 UCHL3 CCAAUUAACCAUGGUGAAA NM_006002 2568 UCHL3 GAACUAAGAUUUAAUGCGA NM_006002 2569 UCHL3 CCAUAGAAGUUUGCAAGAA NM_006002 2570 UCHL3 CAGUAUAUUUCAUGAAGCA NM_006002 2571 UCHL3 AAAUAAAAUCUCAGGGACA NM_006002 2572 UCHL3 GAAGUUUGCAAGAAGUUUA NM_006002 2573 UCHL3 ACCAAGUAUAGAUGAGAAA NM_006002 2574 UCHL3 GCGCGACCCUGAUGAACUA NM_006002 2575 UCHL3 UGGAACAAUUGGACUGAUU NM_006002 2576 UCHL3 UCAGAACAGAAGAGGAAGA NM_006002 2577 UCHL3 GUCAAUGAGCCCUGAAGAA NM_006002 2578 UCHL3 CAAGUAUAGAUGAGAAAGU NM_006002 2579 UCHL3 CAAUAAUGGAAACACCAAA NM_006002 2580 UCHL3 GCACUUUGAAUCUGGAUCA NM_006002 2581 UCHL3 ACAAUAAAGACAAGAUGCA NM_006002 2582 UCHL3 GCAAUUCGUUGAUGUAUAU NM_006002 2583 UCHL3 GUAUAGAUGAGAAAGUAGA NM_006002 2584 UCHL3 CACCAAGUAUAGAUGAGAA NM_006002 2585 UCHL3 GAACAAUUGGACUGAUUCA NM_006002 2586 UCHL3 UCGUUGAUGUAUAUGGAAU NM_006002 2587 UCHL3 UGAAACUAGUGAUGAAACU NM_006002 2588 UCHL3 AGACUGAGGCACCAAGUAU NM_006002 2589 UCHL5 GUUUAGAGCCUGAGAAUUU NM_015984 2590 UCHL5 GCAGAAGAUAGCAGAGUUA NM_015984 2591 UCHL5 GGAUACAGAUCAAGGUAAU NM_015984 2592 UCHL5 GCAAAGAAAGCUCAGGAAA NM_015984 2593 UCHL5 UGAAGAAGAAGUACAGAAA NM_015984 2594 UCHL5 GUACAGUGAAGGUGAAAUU NM_015984 2595 UCHL5 GUUAAUACCACUAGUAGAA NM_015984 2596 UCHL5 GCUUAUUGAAGAAGAAGUA NM_015984 2597 UCHL5 GUAGAAAAGGCAAAAGAAA NM_015984 2598 UCHL5 GAGCCCAAGUAGAAGAAAU NM_015984 2599 UCHL5 GCACAAACGAUAUUCCUUA NM_015984 2600 UCHL5 UAGCAGAGUUACAAAGACA NM_015984 2601 UCHL5 UAAAGAACUUAGAGCAACA NM_015984 2602 UCHL5 CAAAGAAAGCUCAGGAAAC NM_015984 2603 UCHL5 GAUUAAACUGGUUGUCUUA NM_015984 2604 UCHL5 CCGAGGAGCCCAAGUAGAA NM_015984 2605 UCHL5 GAGUUUAGAGCCUGAGAAU NM_015984 2606 UCHL5 AGCCAUAGUGAGUGUGUUA NM_015984 2607 UCHL5 GAGGAGGAACCCAUGGAUA NM_015984 2608 UCHL5 AGAAGGACCGAUUGAUUUA NM_015984 2609 UCHL5 GAGCAAUUCAGAUGUGAUU NM_015984 2610 UCHL5 GUUAAGUGCUAUUCAGUCA NM_015984 2611 UCHL5 AGCCCAAGUAGAAGAAAUA NM_015984 2612 UCHL5 UCAGAUGCUUAUUGAAGAA NM_015984 2613 UCHL5 UGAUAUAUGAGCAGAAGAU NM_015984 2614 UCHL5 GAGAAGGACCGAUUGAUUU NM_015984 2615 UCHL5 AGAUGUGAUUCGACAAGUA NM_015984 2616 UCHL5 CAGUAAGGCCUGUCAUAGA NM_015984 2617 UCHL5 GAUGCUUAUUGAAGAAGAA NM_015984 2618 UCHL5 GAUACGAAGACAUCAGCAA NM_015984 2619 UEV3 GGGCAAAUCAUGAGAAUAA NM_018314 2620 UEV3 AGAAAGACCUGCUGAAUUU NM_018314 2621 UEV3 CAACAGGGAUAUUAUGAUA NM_018314 2622 UEV3 CGAGCAAGGAGAAGACAAA NM_018314 2623 UEV3 GCAAAGAAGUAUGGGUUAU NM_018314 2624 UEV3 AAGAAGAAGUAGUGAGUCU NM_018314 2625 UEV3 GGCACAGACUUCAGGCAAA NM_018314 2626 UEV3 GGACCUAACUGUGGAAGAA NM_018314 2627 UEV3 GGCAAAGAAGUAUGGGUUA NM_018314 2628 UEV3 UCACAGAGAUUACAGUAUA NM_018314 2629 UEV3 GAUCGGAAUUGGAUGUAAU NM_018314 2630 UEV3 UGGGAAUCUUAGUCGGAAA NM_018314 2631 UEV3 UUACAAACUGCUUGGUUAA NM_018314 2632 UEV3 CAGUGGAAAUCAUGACCUA NM_018314 2633 UEV3 GUACAGAGCAAUGUGGAUA NM_018314 2634 UEV3 GUAGAGGGUUUCUUGAUUA NM_018314 2635 UEV3 CAGAAAGACCUGCUGAAUU NM_018314 2636 UEV3 CGGUAUUGCCUGCACAUUA NM_018314 2637 UEV3 GCUCAAGGCAGAAUAUAUU NM_018314 2638 UEV3 UUUACAAACUGCUUGGUUA NM_018314 2639 UEV3 AGAAAUGAUUGCCAAGUUU NM_018314 2640 UEV3 CAUCUCAACCAGUGGAAAU NM_018314 2641 UEV3 CCAAGAAGAAGUAGUGAGU NM_018314 2642 UEV3 AAUUCAAAGAGCUGGGCAA NM_018314 2643 UEV3 AGGCAAAGAAGUAUGGGUU NM_018314 2644 UEV3 GAAAGAAGAUACAGUUACU NM_018314 2645 UEV3 GGUUGGAGGUGGAGAACUC NM_018314 2646 UEV3 UUGAUGUGGUACAGAGCAA NM_018314 2647 UEV3 CCAAUUCGUUUCUGGAUUU NM_018314 2648 UEV3 GCAGAAUAUAUUUGCCCUA NM_018314 2649 UFD1L GCAAUAGACUGGAUGGAAA NM_005659 2650 UFD1L GGAUGAAGCUGGAGGCAGA NM_005659 2651 UFD1L GAGAAAGGAGGGAAGAUAA NM_005659 2652 UFD1L ACAAAGAACCCGAAAGACA NM_005659 2653 UFD1L GGAGAAAGGAGGGAAGAUA NM_005659 2654 UFD1L AAUCAAGCCUGGAGAUAUU NM_005659 2655 UFD1L GGAAGAAAGCCCUAAGUGA NM_005659 2656 UFD1L CUACAAAGAACCCGAAAGA NM_005659 2657 UFD1L CAAAGAACCCGAAAGACAA NM_005659 2658 UFD1L GGACAGUCAUUGCGUAAAA NM_005659 2659 UFD1L AGAAAGGAGGGAAGAUAAU NM_005659 2660 UFD1L GGUCAGAUGUGGAGAAAGG NM_005659 2661 UFD1L GGAGAUAUUAAAAGAGGAA NM_005659 2662 UFD1L CCAAUCAAGCCUGGAGAUA NM_005659 2663 UFD1L CGACAGAAGGUGAAGCCGA NM_005659 2664 UFD1L GCCAUCAACUAUAAUGAAA NM_005659 2665 UFD1L UGUUCAAACUGACCAAUAA NM_005659 2666 UFD1L AAAGACAAGUCCAGCAUGA NM_005659 2667 UFD1L AAAGGAGGGAAGAUAAUUA NM_005659 2668 UFD1L CCAAAGCCGUAUUAGAAAA NM_005659 2669 UFD1L AAGGACAGUCAUUGCGUAA NM_005659 2670 UFD1L CAAACUGACCAAUAAGAAU NM_005659 2671 UFD1L ACUGUUGGCUGAUUGGAAA NM_005659 2672 UFD1L CAGGUCAGAUGUGGAGAAA NM_005659 2673 UFD1L GGUAAGAUAACUUUCAUCA NM_005659 2674 UFD1L CCCAAAGCCGUAUUAGAAA NM_005659 2675 UFD1L CGAAAGACAAGUCCAGCAU NM_005659 2676 UFD1L GUGACAUGAACGUGGACUU NM_005659 2677 UFD1L UGGAAAGAAGAAAGGGGUA NM_005659 2678 UFD1L CAUGAGGAGUCGACAGAAG NM_005659 2679 USP1 AAACAAAGGUGAAGAACAA NM_003368 2680 USP1 GAAGAGAACCAGAGACAAA NM_003368 2681 USP1 GCAUAGAGAUGGACAGUAU NM_003368 2682 USP1 AGAAAGGAUUGUAGGAGAA NM_003368 2683 USP1 AAUUAGAGUUGGUGGAAAU NM_003368 2684 USP1 AGAAAUACCUCAUCCGAAA NM_003368 2685 USP1 GAAAGAAGCUCUAAAGGAU NM_003368 2686 USP1 GAUUGUAGGAGAAGAUAAA NM_003368 2687 USP1 GGGAAACAUUCAAGAAACA NM_003368 2688 USP1 GUUUUGAGCUAGUGGAGAA NM_003368 2689 USP1 UGACCAAAUGUGUGAAAUA NM_003368 2690 USP1 GGUUAAAGUCUGCAACUAA NM_003368 2691 USP1 CCAAGGAGUCAAAGGACAA NM_003368 2692 USP1 GGGAAGUGUGAAAGUGAUA NM_003368 2693 USP1 GGUUUUAAAUCUGGAGUAA NM_003368 2694 USP1 GUGCAAAGCUUAAAGGAGU NM_003368 2695 USP1 CUAGAAGAAUGGAGCACAA NM_003368 2696 USP1 GAGACAAACUAGAUCAAAA NM_003368 2697 USP1 GAAUAUAGAGCAUCUGAAA NM_003368 2698 USP1 UGGAAGAGAACCAGAGACA NM_003368 2699 USP1 UGUAGAAGCUAUUGGACUU NM_003368 2700 USP1 CAAAGCAGAUUAUGAGCUA NM_003368 2701 USP1 CUGAAGACUUUAAAGAGAA NM_003368 2702 USP1 GGGAAAUUGCAAAGAAGAU NM_003368 2703 USP1 AGUCAAAGGACAAUCUAAA NM_003368 2704 USP1 GGAAAUACACAGCCAAGUA NM_003368 2705 USP1 UGUCAUACCUAGUGAAAGU NM_003368 2706 USP1 UAGAAAGGAUUGUAGGAGA NM_003368 2707 USP1 GGAAGAAAGAAGCUCUAAA NM_003368 2708 USP1 GGGGUGUGGUUGAGAAUUA NM_003368 2709 USP10 AAGAAGAUGCUGAGGAAUA NM_005153 2710 USP10 CAAACAAGAGGUUGAGAUA NM_005153 2711 USP10 GAUAAAAUCGUGAGGGAUA NM_005153 2712 USP10 ACAAGAAGAUGCUGAGGAA NM_005153 2713 USP10 GAGAUAAGAAAGUGGAUUU NM_005153 2714 USP10 CCACAGAAGCCCUGGUCAA NM_005153 2715 USP10 GAGGAAAUGUUGAACCUAA NM_005153 2716 USP10 GAGAUAAGUCGAAGAGUGA NM_005153 2717 USP10 GGACAAAGGGAGCGUAAAA NM_005153 2718 USP10 GGACAAGAAUAUCAGAGAA NM_005153 2719 USP10 GACAAGAAUAUCAGAGAAU NM_005153 2720 USP10 AAGAAGAGCAGGAAGAACA NM_005153 2721 USP10 AGGAAAUGUUGAACCUAAA NM_005153 2722 USP10 CCAUAAAGAUUGCAGAGUU NM_005153 2723 USP10 GAGAAUCUGUCCAAGGUUA NM_005153 2724 USP10 AUGCAGAAUUUAUGGGUGA NM_005153 2725 USP10 CAGCCUACCUCCUGUAUUA NM_005153 2726 USP10 UUGCAGAGUUGCUGGAGAA NM_005153 2727 USP10 UAAACUACCUGAUGGACAA NM_005153 2728 USP10 AUGAAGAAGAGCAGGAAGA NM_005153 2729 USP10 GCAGGAAGAACAAGGUGAA NM_005153 2730 USP10 GGAAGAACAAGGUGAAGGA NM_005153 2731 USP10 GGGAACUGGUGCUACAUUA NM_005153 2732 USP10 UGGAGUUGCUAAUGGACAA NM_005153 2733 USP10 CAGCAGAGUUCAAAAGAAU NM_005153 2734 USP10 GGAAAUUAGUAAAGAACUG NM_005153 2735 USP10 UGAAAAGGGUCGACAAGAA NM_005153 2736 USP10 CCACAUAUAUUUACAGACU NM_005153 2737 USP10 GGACUUGGAAAUUAGUAAA NM_005153 2738 USP10 GUGAAGGAAGCGAGGAUGA NM_005153 2739 USP11 AGGUAGAGGCUGAGGGCUA NM_004651 2740 USP11 CGGAAGAGGAUGAGGACUU NM_004651 2741 USP11 GGGUGAAGAAGAAGGAGUA NM_004651 2742 USP11 AAGAUGACGAGGAGGAUAA NM_004651 2743 USP11 GUGGAGAAGCACUGGUAUA NM_004651 2744 USP11 UCAGAAGGCUCUUUGGAUA NM_004651 2745 USP11 GCACAGGAGGCAUGGCAAA NM_004651 2746 USP11 UGGUGGAAGGCGAGGAUUA NM_004651 2747 USP11 CAGAGAUGAAGAAGCGUUA NM_004651 2748 USP11 GGGAUGAGAAAGAAGAUGA NM_004651 2749 USP11 GAACAAGGUUGGCCAUUUU NM_004651 2750 USP11 GGACGAUGGGGAUGAGAAA NM_004651 2751 USP11 GAGAUAAACUGGCGCCUCA NM_004651 2752 USP11 UGUAUAACGUCCUGAUGUA NM_004651 2753 USP11 AGAAAGAAGAUGACGAGGA NM_004651 2754 USP11 ACAACAACAUGUCGGAAGA NM_004651 2755 USP11 AGAAUCAGAUCGAGUCCAA NM_004651 2756 USP11 GCUGGUUCCUUGUGGAGAA NM_004651 2757 USP11 GGCACAAUGAUUUGGGCAA NM_004651 2758 USP11 AUGACGAGGUAGAGGCUGA NM_004651 2759 USP11 CCGAGUACUUCCUCAACAA NM_004651 2760 USP11 GCUCUGAGUUCAUGGAUGU NM_004651 2761 USP11 AUGCAGACCUGGUGAAGCA NM_004651 2762 USP11 GGCACUACUUUGAUGACAA NM_004651 2763 USP11 CUGGUAUGGUCUAGAGCAU NM_004651 2764 USP11 AAGAAGAUGACGAGGAGGA NM_004651 2765 USP11 GGGCAUGAAGGGUGAGAUC NM_004651 2766 USP11 GUUACUAUGACGAGGUAGA NM_004651 2767 USP11 GUUCAUGGAUGUUAAUUGA NM_004651 2768 USP11 GUGAGAUCGCAGAGGCCUA NM_004651 2769 USP12 CAGCAAAGAUGAAGAUUUU NM_182488 2770 USP12 CCUAAGAAGUUCAUCACAA NM_182488 2771 USP12 GAAGAGAGAAAGCAGGAAA NM_182488 2772 USP12 CAUCACAAGAUUACGGAAA NM_182488 2773 USP12 UUGCAAUAGUUAAGAGUCA NM_182488 2774 USP12 CCACCAAUCCAGACAGAAU NM_182488 2775 USP12 GCAGCAAAGAUGAAGAUUU NM_182488 2776 USP12 ACAAGAUUACGGAAAGAAA NM_182488 2777 USP12 UGCACAAGCUAUUGAAGAA NM_182488 2778 USP12 GGAUCAACUUCAUCGAUAU NM_182488 2779 USP12 CACAAACGGAUGAAAGUUA NM_182488 2780 USP12 GAAAGAGAUUGGUCCAGAA NM_182488 2781 USP12 ACAAACGGAUGAAAGUUAA NM_182488 2782 USP12 GCGUAUAAGAGUCAACCUA NM_182488 2783 USP12 CAGAACAGUUUCCGGUCAA NM_182488 2784 USP12 CAUCAGAUAUCUCAAAGAA NM_182488 2785 USP12 GGCAUUAGAGAAAGAGAUU NM_182488 2786 USP12 GCCCAUGAUUCUAGCUCUA NM_182488 2787 USP12 GCAAACAGGAAGCACACAA NM_182488 2788 USP12 GCAACAAGAUGCCCAUGAA NM_182488 2789 USP12 UGGAUCAACUUCAUCGAUA NM_182488 2790 USP12 GCAUAGCCACUCAGAAGAA NM_182488 2791 USP12 GUUUAACACUUCAGGUGAU NM_182488 2792 USP12 CAAACAGGAAGCACACAAA NM_182488 2793 USP12 GAUCAACUUCAUCGAUAUA NM_182488 2794 USP12 GCAGCAAACAGGAAGCACA NM_182488 2795 USP12 UGAAGAGUGUCGCAGCAAA NM_182488 2796 USP12 UUGAAGAAUUCUACGGGUU NM_182488 2797 USP12 CGGCAUUAGAGAAAGAGAU NM_182488 2798 USP12 UCAAUUACUCACUGCUUAA NM_182488 2799 USP13 UGAUUGAGAUGGAGAAUAA NM_003940 2800 USP13 GCACGAAACUGAAGCCAAU NM_003940 2801 USP13 GGGAACAUGUUGAAAGACA NM_003940 2802 USP13 GGUCAUUACAUUUGCCAUA NM_003940 2803 USP13 AGAAUGGGCUCCAGGACAA NM_003940 2804 USP13 AGACAGUGAUUUUGUGAUU NM_003940 2805 USP13 UGAUGAAGGAGGAGCACAA NM_003940 2806 USP13 AUAUGAAGAUGAAGCCAAA NM_003940 2807 USP13 GAAGGGAAGCAGAAGCAAA NM_003940 2808 USP13 GCGACAGGGUCUACAAGAA NM_003940 2809 USP13 UGAAAUAGCACUACCAAAU NM_003940 2810 USP13 GGACAAUGGAGUCAGGAUU NM_003940 2811 USP13 ACACGGAGAGGGUGGAUUA NM_003940 2812 USP13 UGAAGAAGACAGUGAUUUU NM_003940 2813 USP13 GAGAAUAAUGCCAAUGCAA NM_003940 2814 USP13 GGAUGGAUCUGGAACAUAU NM_003940 2815 USP13 ACGAAUAAUAACCUGGAAA NM_003940 2816 USP13 AGAAUAAUGCCAAUGCAAA NM_003940 2817 USP13 ACUUGGUAGUGCAGAUAAA NM_003940 2818 USP13 AGGAUGAACUGAUCGCUUA NM_003940 2819 USP13 GGGCAGAUGUUUAUUCUUU NM_003940 2820 USP13 GUUACAGCCAGGAGAGGAA NM_003940 2821 USP13 GCACUGGAUUGGAUCUUUA NM_003940 2822 USP13 GGAAGAUGGCUGCAGGAGA NM_003940 2823 USP13 UGAACUAACGAGAAGGGAA NM_003940 2824 USP13 GAAGAUGGGUGAUUUACAA NM_003940 2825 USP13 AGGAGGAAUUCCAAGAUUU NM_003940 2826 USP13 CAGAGGAAAUCGUAGCUAU NM_003940 2827 USP13 GCUUAUGAACUAACGAGAA NM_003940 2828 USP13 GGAAGGAAGAUGGGUGAUU NM_003940 2829 USP14 GGAGAAAUUUGAAGGUGUA NM_005151 2830 USP14 GGAUUAAGUUUGAUGAUGA NM_005151 2831 USP14 UGAAAUAAUGGAAGAGGAA NM_005151 2832 USP14 GAAACAAGAUGAAUGGAUU NM_005151 2833 USP14 AGAGGAAAGUGAACAGUAA NM_005151 2834 USP14 GGUGAAAGGAGGAACGCUA NM_005151 2835 USP14 GCCAAAUACAAGUGACAAA NM_005151 2836 USP14 GAGUAUUGCAACAGAAAUU NM_005151 2837 USP14 ACCAGAACUUCAAGAGAAA NM_005151 2838 USP14 CCAGAAAGAAGUUAAGUAU NM_005151 2839 USP14 GAGUUGAAAUAAUGGAAGA NM_005151 2840 USP14 ACAGAAAGUUAUGGUGAAA NM_005151 2841 USP14 CAACAGAAAUUGGAAGCAA NM_005151 2842 USP14 CGAGAAAGGUGAACAAGGA NM_005151 2843 USP14 AUCCAGAGCUUUAGAGGAA NM_005151 2844 USP14 AGAAGAACCCUCAGCCAAA NM_005151 2845 USP14 GAGGAACGCUAAAGGAUGA NM_005151 2846 USP14 CACCAGAACUUCAAGAGAA NM_005151 2847 USP14 GACAGAAAGUUAUGGUGAA NM_005151 2848 USP14 GCUGAAGACAUGUUUAAUA NM_005151 2849 USP14 GCUAAUGAAUGUUGGAUAC NM_005151 2850 USP14 GCAAAGAAAUGCCUUGUAU NM_005151 2851 USP14 CAUGAAAUGUACAGAAUCU NM_005151 2852 USP14 GAAAUUUGAAGGUGUAGAA NM_005151 2853 USP14 GCAGGUGCCUUGAGAGCUU NM_005151 2854 USP14 CCAAAGUUCUUAAGGAUGU NM_005151 2855 USP14 UCUAUAAUCCAGAGCUUUA NM_005151 2856 USP14 GCGAGUAUUGCAACAGAAA NM_005151 2857 USP14 CUUGAGAGCUUCAGGGGAA NM_005151 2858 USP14 GGAUACAAAUGAUGCGAGU NM_005151 2859 USP15 GGAACAAAUACAUGAGUAA NM_006313 2860 USP15 GCAGAUAAGAUGAUAGUUA NM_006313 2861 USP15 AGGAAUGAGAGGUGAAAUA NM_006313 2862 USP15 GCAUAAACACCUUGAAUUU NM_006313 2863 USP15 GAAUUGAAGCUAUGUGAAA NM_006313 2864 USP15 AUGAAAGUGUGGAGUAUAA NM_006313 2865 USP15 GAUUUUAACUUGUGCAGUA NM_006313 2866 USP15 GGAAACAGGUUCUAGAUUU NM_006313 2867 USP15 ACAAAUACCAGAUGGGAGA NM_006313 2868 USP15 CAUUUGAACCACUGAAUAA NM_006313 2869 USP15 GAAACAAUACUGAAGACAA NM_006313 2870 USP15 UAGCAAAGCUGACACAAUA NM_006313 2871 USP15 GAUGUGAGUUGAUGACAAA NM_006313 2872 USP15 CUGCAAAGUAGAAGUAUAU NM_006313 2873 USP15 GGAGAUAAUGAUUCUGAAA NM_006313 2874 USP15 AUACAGAGCACGUGAUUAU NM_006313 2875 USP15 ACACAUUGAUGGAAGGUCA NM_006313 2876 USP15 ACUGCAAAGUAGAAGUAUA NM_006313 2877 USP15 CCUGUUUGCCUAAGAGAAA NM_006313 2878 USP15 GAUGGAAGGUCAAGAGCCA NM_006313 2879 USP15 GAGACCAGAUUGUGGAACA NM_006313 2880 USP15 UGUUGUAACUCGAAGAUUU NM_006313 2881 USP15 AAGCAAAUGUGGUCUGGAA NM_006313 2882 USP15 ACAAUUGGCUAUAAAGGUA NM_006313 2883 USP15 UCAGAUAACCGAAUGUAAA NM_006313 2884 USP15 GAAUAUUCGCUAUGGAUGA NM_006313 2885 USP15 GCAGAUGGAAGGCCAGAUA NM_006313 2886 USP15 AGGACAGGUAUUAGUGAUA NM_006313 2887 USP15 UCAGCAAGCCACAAAGAAA NM_006313 2888 USP15 CCGAACUGAUCAAGCAAAU NM_006313 2889 USP16 AGAUAAAGCUGAAGAAGAA NM_006447 2890 USP16 GGAACAAGGUAAUUUGAAA NM_006447 2891 USP16 AAACAUGGCUAAAGAGAAU NM_006447 2892 USP16 AGAUCAAGAUAGUGAGGAA NM_006447 2893 USP16 CAGAGAAAGAUAAUGGAAA NM_006447 2894 USP16 AAGAGUGAGUAAAGGAAUA NM_006447 2895 USP16 CCACAGAGGAAGUAGAUAU NM_006447 2896 USP16 AGAAUGAACAAGAGAGAGA NM_006447 2897 USP16 UGAUCAGAGUGGUAAGAAA NM_006447 2898 USP16 CAUCUUUGGUGGUGAACUA NM_006447 2899 USP16 AGAAACGGACAAAGGGAAA NM_006447 2900 USP16 GUUCAAACCAGUUGGGUCA NM_006447 2901 USP16 GACCAAAGGCAAAUAUAAA NM_006447 2902 USP16 GGACCAAAGGCAAAUAUAA NM_006447 2903 USP16 GGAUGAAGAUCAAGAUAGU NM_006447 2904 USP16 UGAAGAAGAAACAGAAGAA NM_006447 2905 USP16 GUAAUGGACCAAAGGCAAA NM_006447 2906 USP16 GUGAAUGUGGAAUGGAAUA NM_006447 2907 USP16 UAAGAAUGUUGCAGAAGAA NM_006447 2908 USP16 AGUGAAAGAUAAAGCUGAA NM_006447 2909 USP16 GAACAAAGGUGUAUGAGGU NM_006447 2910 USP16 GAACCAACGAAGACAACAA NM_006447 2911 USP16 GUGAAAGGACUCAGUAAUU NM_006447 2912 USP16 CAGAGGAAGUAGAUAUGAA NM_006447 2913 USP16 GGAAGGGAGCAAUGGAGAA NM_006447 2914 USP16 AAGAUAAAGCUGAAGAAGA NM_006447 2915 USP16 AGAGAGAAAAGAAGGAAAA NM_006447 2916 USP16 GAAAGAUAAAGCUGAAGAA NM_006447 2917 USP16 CGAAUAAACUGCUUUGUGA NM_006447 2918 USP16 CUGUAAGACUGACAAUAAA NM_006447 2919 USP18 GAAGAAGACCCGUGGGAAA NM_017414 2920 USP18 GGACAGACCUGCUGCCUUA NM_017414 2921 USP18 CUGCAUAUCUUCUGGUUUA NM_017414 2922 USP18 ACAUGAAGAUGGAGUGCUA NM_017414 2923 USP18 CCAUAUGAAUCAAGUGUUU NM_017414 2924 USP18 GCAUGGCGCUUGAGAGAUU NM_017414 2925 USP18 GGAAUGCUGUGGAUGGAAA NM_017414 2926 USP18 UCCAUAAGAUAGUGUGAUA NM_017414 2927 USP18 AGAAGGAAGAAGACAGCAA NM_017414 2928 USP18 GGAAACAGGUCUUGAAGCU NM_017414 2929 USP18 GGAAUUCACAGACGAGAAA NM_017414 2930 USP18 UAAACACGGUCAUGAAUAA NM_017414 2931 USP18 CCCAAAACCUUCAGAGAUU NM_017414 2932 USP18 GGAAAAUGGUCUUGCUUCA NM_017414 2933 USP18 ACAGCAACAUGAAGAGAGA NM_017414 2934 USP18 GGGAAGACAUCCAGUGUAC NM_017414 2935 USP18 GACAUUAGCCCUUUAGUUA NM_017414 2936 USP18 GGAAAAUGGUUCUGCUUCA NM_017414 2937 USP18 GCUGACGAGCAGAGGAGAA NM_017414 2938 USP18 AAGAAAAGAAGGAAGAAGA NM_017414 2939 USP18 CCAGGAUAUUGAAGAGGAU NM_017414 2940 USP18 UGAUAAACACGGUCAUGAA NM_017414 2941 USP18 CCAACAUGAUGCUGCCCAA NM_017414 2942 USP18 GGAGAAGCAUUGUUUUCAA NM_017414 2943 USP18 CCAGGGAGUUAUCAAGCAA NM_017414 2944 USP18 AGGAAUUCACAGACGAGAA NM_017414 2945 USP18 GGGAAGAAGACCCGUGGGA NM_017414 2946 USP18 GAGAAGCAUUGUUUUCAAA NM_017414 2947 USP18 UCGUAAUGAAUGUGGACUU NM_017414 2948 USP18 AGGAUAUUGAAGAGGAUCA NM_017414 2949 USP2 CGACAGAUGUGGAGAAAAU NM_004205 2950 USP2 CUGAAUACCUGGUCGACUA NM_004205 2951 USP2 AGACCCAGAUCCAGAGAUA NM_004205 2952 USP2 UCGACUACCUGGAGAACUA NM_004205 2953 USP2 CCAAAGAGGAUGUGCUUGA NM_004205 2954 USP2 GAAGGGACAUCUUUGGAAA NM_004205 2955 USP2 GGGAAGAGACGGCAUGAAU NM_004205 2956 USP2 ACACAAACCUGACAAGAGA NM_004205 2957 USP2 CGAGAAAGGCCGACAGAUG NM_004205 2958 USP2 CUGCAGUGCCUGAGCAACA NM_004205 2959 USP2 GCAUGAGGCUCUUCACCAA NM_171997 2960 USP2 ACACAGCCCUCGUGGAAGA NM_004205 2961 USP2 GACCUGGACUUAAGAGAAU NM_004205 2962 USP2 GGAAGAGACGGCAUGAAUU NM_004205 2963 USP2 AGGAUGUGCUUGAUGGAGA NM_171997 2964 USP2 CGGCAUGAAUUCUAAGAGU NM_004205 2965 USP2 CUGAAGCGCUACACAGAAU NM_004205 2966 USP2 GAAAAUAUCUAGAACGGGA NM_004205 2967 USP2 UCGCUGACGUGUACAGAUU NM_004205 2968 USP2 UGACAUUAAUGGACUGCAU NM_004205 2969 USP2 ACAAACCUGACAAGAGAAA NM_004205 2970 USP2 GGCAGAAAACGGUGUAUAA NM_004205 2971 USP2 UAACUAAAGUGUUCAGACU NM_004205 2972 USP2 CAUCUGAGUUCAAGACCCA NM_004205 2973 USP2 GCCGACAGAUGUGGAGAAA NM_004205 2974 USP2 GGAUGUGCUUGAUGGAGAU NM_004205 2975 USP2 ACACACAGCCCUCGUGGAA NM_171997 2976 USP2 AGAAAACGGUGUAUAAAGA NM_171997 2977 USP2 CGAGGUGAACCGAGUGACA NM_171997 2978 USP2 UCAACAAAGCCAAGAAUUC NM_171997 2979 USP20 GGACAAUGAUGCUCACCUA NM_006676 2980 USP20 CUGAUGAGUUAAAGGGUGA NM_006676 2981 USP20 GGUCAAAGGAAGCGGCCAU NM_006676 2982 USP20 CCAUAGGAGAGGUGACCAA NM_006676 2983 USP20 UCAAGAAAGCCCAGGUAUU NM_006676 2984 USP20 GGGAGUAGCUGCUGCUUCA NM_006676 2985 USP20 GUACAAACUCGGAGCAAGU NM_006676 2986 USP20 GAAAGGAGGACCUGGCCAA NM_006676 2987 USP20 AGUUAAAGGGUGACAACAU NM_006676 2988 USP20 AUGAGAAACGGGAGGGUGA NM_006676 2989 USP20 GAGUGACACGGAUGAGAAA NM_006676 2990 USP20 GCAUGAAGAACCUCGGGAA NM_006676 2991 USP20 CGCCAGAGCCGGACAAUGA NM_006676 2992 USP20 CGUCGUACGUGCUCAAGAA NM_006676 2993 USP20 GGUGUAAGAAGCUGCGGAA NM_006676 2994 USP20 GGUACGAGUUUGAUGACCA NM_006676 2995 USP20 UGCAGAACGCCGAGGGCUA NM_006676 2996 USP20 GGGCAGAUUUCGGAGGAGA NM_006676 2997 USP20 GUAAAGAGGCAGAAAAGUU NM_006676 2998 USP20 CCUGUGAGAAGGAGGUAUU NM_006676 2999 USP20 GGAACCGGAUGAUGAAACA NM_006676 3000 USP20 GGACCAAACCUAUGGGCCU NM_006676 3001 USP20 CCAUUCAUGCACAGGCAAA NM_006676 3002 USP20 UCUGAAAGCUGUUCCUAUU NM_006676 3003 USP20 AAGCACAACUUGACCGUGA NM_006676 3004 USP20 ACGAGACGGUGGUGCAGAA NM_006676 3005 USP20 CUGCUCAAAUCUAAGGGAA NM_006676 3006 USP20 GAGCUGAUGCUAAAGAAGA NM_006676 3007 USP20 CGAGUGACACGGAUGAGAA NM_006676 3008 USP20 UCUCUGAGGUCUGGCAUAA NM_006676 3009 USP21 GCUAGAAGAACCUGAGUUA NM_012475 3010 USP21 GAGCUGUCUUCCAGAAAUA NM_012475 3011 USP21 GAGCCAACCUAAUGUGGAA NM_016572 3012 USP21 GUGCCAGGCCUGUGGGUAU NM_012475 3013 USP21 AAGAAGAGCUAGAGUCGGA NM_016572 3014 USP21 GUUUCAACCUUUUCACUAA NM_012475 3015 USP21 GGUUGUAGCUCCAUUAUUU NM_016572 3016 USP21 CACUAAGGAAGAAGAGCUA NM_012475 3017 USP21 CUAAGGAAGAAGAGCUAGA NM_016572 3018 USP21 CGGCAGAAAACUCGAAGUA NM_012475 3019 USP21 GUACAAAGAUUCCCUCGAA NM_012475 3020 USP21 UGAUGAACGGCUCAAGAAA NM_012475 3021 USP21 CCACCCACUUUGAGACGUA NM_012475 3022 USP21 GCGAGAGGACAGCAAGAUU NM_016572 3023 USP21 CUGUGAAGCCCUUUAAACA NM_012475 3024 USP21 GUUAAGUGAUGAUGACCGA NM_016572 3025 USP21 GAGCGAGAGGACAGCAAGA NM_012475 3026 USP21 CCUCAGAGACGUCUAUUUU NM_012475 3027 USP21 GCAGCAAGGAGCGCAGAAA NM_012475 3028 USP21 GCGCAGAAACCCAGCCUCU NM_012475 3029 USP21 UAGAAGAACCUGAGUUAAG NM_012475 3030 USP21 CUUCGAAACCUGGGAAACA NM_012475 3031 USP21 GAACCUGAGUUAAGUGAUG NM_012475 3032 USP21 UGGCAUCCAGCGAGGGCUA NM_012475 3033 USP21 AGUUGACAGUACAAAGAUU NM_016572 3034 USP21 UUCAGUAGGUGUAGACUUU NM_016572 3035 USP21 GCAGGAUGCCCAAGAGUUC NM_012475 3036 USP21 CGGGAUUGUUUCAACCUUU NM_016572 3037 USP21 CUGAUGAACGGCUCAAGAA NM_016572 3038 USP21 AUGAACGGCUCAAGAAACU NM_016572 3039 USP22 CUGCAAAGGUGAUGACAAU XM_042698 3040 USP22 CCAAGGAGGAGCAGCGAAA XM_042698 3041 USP22 UGACAAAGACAUGGAAAUA XM_042698 3042 USP22 GGACUACAUCUAUGACAAA XM_042698 3043 USP22 CCACAAAGCAGCUCACUAU XM_042698 3044 USP22 CAGCGAAAAGCUUGGAAAA XM_042698 3045 USP22 GCAAACCGGUUCAGUGCUA XM_042698 3046 USP22 AUGACAAAGACAUGGAAAU XM_042698 3047 USP22 GCGAGGGCAACGUGGUAAA XM_042698 3048 USP22 AGGACUACAUCUAUGACAA XM_042698 3049 USP22 CAACAAUGACAACAAGUAU XM_042698 3050 USP22 ACUGAGAGCCUAUGACAAU XM_042698 3051 USP22 CAACCAAACGGGAGCUUGA XM_042698 3052 USP22 CCGAAAAGGAGAAAGAUCA XM_042698 3053 USP22 GGAGAAAGAUCACCUCGAA XM_042698 3054 USP22 GUGGACAACUGGAAGCAGA XM_042698 3055 USP22 AGCAAAGAGAGCAGGAUGA XM_042698 3056 USP22 GCAAAGAGAGCAGGAUGAA XM_042698 3057 USP22 GCAGCAGCGCCAAGAUCAA XM_042698 3058 USP22 GACAAAGACAUGGAAAUAA XM_042698 3059 USP22 UCACAAAGAAGCAUAUUCA XM_042698 3060 USP22 CGGACAGUCUCAACAAUGA XM_042698 3061 USP22 GCAAGGCGUUGGAGAGAAG XM_042698 3062 USP22 GCAGCUUCAAGGUGGACAA XM_042698 3063 USP22 CCUCACUGUUUCAGGAGUU XM_042698 3064 USP22 AAAUAAUCGCCAAGGAGGA XM_042698 3065 USP22 GCAUCAUAGACCAGAUCUU XM_042698 3066 USP22 UCAACAAUGACAACAAGUA XM_042698 3067 USP22 GAAGCAUAUUCACGAGCAU XM_042698 3068 USP22 GAGCGAGGGCAACGUGGUA XM_042698 3069 USP24 CCAACUACUUCAUGAAAUA XM_165973 3070 USP24 CCUCAUGAGUUAAAGAAUA XM_165973 3071 USP24 CUAUAGAGGCUCACAGUAA XM_165973 3072 USP24 UGACACAGUUAUAGAAGAA XM_165973 3073 USP24 GAACAAAUCCUUACAGUGA XM_165973 3074 USP24 GAAUGUUGCUCCUGGCAUA XM_165973 3075 USP24 GGACGAGAAUUGAUAAAGA XM_165973 3076 USP24 GAGAUUACUUGGCUGGAUA XM_165973 3077 USP24 GAGAACAGCAGGAUGCAUA XM_165973 3078 USP24 GCCAAAUCCUUCUGUGAAA XM_165973 3079 USP24 GGGAGUAGCCAGCCAAUUA XM_165973 3080 USP24 GGAUGAAUACCUCAAGAAA XM_165973 3081 USP24 AAAGCAAGCUGCAGUACUA XM_165973 3082 USP24 GAAAAUGCCUGCUCGAAUA XM_165973 3083 USP24 CUACGAUGCUUGAAGAUGA XM_165973 3084 USP24 GAAUAGAGAUGUAUACAGU XM_165973 3085 USP24 AGAAGAAGAUGUCAGAACA XM_165973 3086 USP24 GGAAAUGCUUGGUUCAUCA XM_165973 3087 USP24 GGGAAUCUGUGUUCGACAA XM_165973 3088 USP24 CAACUUGAUUCUUUAGGAA XM_165973 3089 USP24 UUGAUCAGAUGGAUGAAUA XM_165973 3090 USP24 UGACAGUAAUGAAACCAUA XM_165973 3091 USP24 GUUCUAAGCUCCAAACUCA XM_165973 3092 USP24 CGAAACAGACUCAGCAGUU XM_165973 3093 USP24 GAAAAGGACCUGUAUUAAA XM_165973 3094 USP24 AAACAAACCCAUACACUGA XM_165973 3095 USP24 GAAAAGAGAAUAACAGUGA XM_165973 3096 USP24 AGGGAAACCUUACCUGUUA XM_165973 3097 USP24 CCACAGCUUUGUUGAAUGA XM_165973 3098 USP24 UUACCAAGGAGUUUGAUUA XM_165973 3099 USP25 GCACAGAAACAGAGAAAUA NM_013396 3100 USP25 UGGAAUAACUGAUGAGGAA NM_013396 3101 USP25 GGGAAGAGCUAGUGAGGGA NM_013396 3102 USP25 GGGAGUACUUGAAGGUAAA NM_013396 3103 USP25 CUGUAGAAGAUAUGAGAAA NM_013396 3104 USP25 GGGAAGAGAUCAAGAGACU NM_013396 3105 USP25 GCUAAAGAAUGUUGGCAAU NM_013396 3106 USP25 GAAAGUUGCUCAAGCCAAA NM_013396 3107 USP25 GAUAAAACCUGAAGAAGUA NM_013396 3108 USP25 AACAAAGGCUAGAAAGAUA NM_013396 3109 USP25 GGCAAUACUUGUUGGUUUA NM_013396 3110 USP25 UAUAGGAAAUUCAGGGAAA NM_013396 3111 USP2S CAUCAGGAUUAUAGGAAAU NM_013396 3112 USP25 CAUUAUUACUGGUGGAUGA NM_013396 3113 USP25 CAGAAAGCUUUGCAGGAAA NM_013396 3114 USP25 ACAGAUACAUGCACAGAAA NM_013396 3115 USP25 GCAGAUGGAUGAAGUACAA NM_013396 3116 USP25 GCAUCAGGAUUAUAGGAAA NM_013396 3117 USP25 GGACAGAAAUAGAAAAUGA NM_013396 3118 USP25 CCAGCAUAGCAGAGAAUAA NM_013396 3119 USP25 GGUAAAUCCAGGAGUGUAU NM_013396 3120 USP25 UGGAGAGGAUCGAGAAGUA NM_013396 3121 USP25 UGGGAGUACUUGAAGGUAA NM_013396 3122 USP25 CCACCGGAUUUGAGAGAUU NM_013396 3123 USP25 CGUGAAAGCAGAUGGAUGA NM_013396 3124 USP25 GAGCAUUGGUUUACUGAAU NM_013396 3125 USP25 GGAAUUUGCCUCAAGUAAA NM_013396 3126 USP25 AGGCAAUUAAGUUGGAAUA NM_013396 3127 USP25 GAACCAGGCACCAAAGAAA NM_013396 3128 USP25 GAGCAAUUGCCUUGAGUUU NM_013396 3129 USP26 CCACAAAGCUGGAGGUAAA NM_031907 3130 USP26 CCACAAAGUUGAUGAGAAA NM_031907 3131 USP26 CAGAAGAGCUUGAGUAUAA NM_031907 3132 USP26 AAGCUAUAAUCGAGAGAAA NM_031907 3133 USP26 ACAAAGGAAUCCAAAGAUA NM_031907 3134 USP26 GAACGAUGCUCAUGAGUUU NM_031907 3135 USP26 GAGUGAGGAUGGAGAAAUU NM_031907 3136 USP26 GGUUACACAAAGUGGGAUA NM_031907 3137 USP26 UAUCAGAAUUCCAGAAAGA NM_031907 3138 USP26 GCACAACACAGAAGGAAAU NM_031907 3139 USP26 CCUAUGACUUUGAGAAACA NM_031907 3140 USP26 GCAAAAGUACCUUGGAAAA NM_031907 3141 USP26 ACACAAAGUGGGAUAAAUU NM_031907 3142 USP26 CAGCACAAGAAGAGGAAAA NM_031907 3143 USP26 CCAAUAAGAAUCCAAGAAA NM_031907 3144 USP26 CCACAGAUGCUGAACAAUU NM_031907 3145 USP26 GCUAUAAUCGAGAGAAACA NM_031907 3146 USP26 UUGAAGCAGUGGAAAGAAA NM_031907 3147 USP26 CCUAAGACCUACAAAAUUA NM_031907 3148 USP26 CUGAAAGAUAACAUGGAAA NM_031907 3149 USP26 CAGAGAUGAAUGAGGAAUU NM_031907 3150 USP26 GAGAAAUCAAGUAGCAAAU NM_031907 3151 USP26 GAAAUGAUGAUAAGGGAGA NM_031907 3152 USP26 GAGAGAAACAAUUGAAGUU NM_031907 3153 USP26 UGGAAAGAAAGAAGAAAGA NM_031907 3154 USP26 CAACAAAGGAAUCCAAAGA NM_031907 3155 USP26 CUGUUUAGAUCAACUGAAA NM_031907 3156 USP26 GAGCAGAAGAGCUUGAGUA NM_031907 3157 USP26 CCGAAAAUCCAAAACGAAA NM_031907 3158 USP26 GCAGAAGACAGCAGCAAAA NM_031907 3159 USP28 GGGAAGAAGUUGAAAGAGA NM_020886 3160 USP28 CCAUUGAGGUCAUGAGAAA NM_020886 3161 USP28 GGACAAGAGCGUUGGUUUA NM_020886 3162 USP28 UGGAAAGGUAUGUGAAAUA NM_020886 3163 USP28 UCACAGAUGAGGAGAUAAA NM_020886 3164 USP28 AAGCGAAACUGAAGGAAAU NM_020886 3165 USP28 GCAAGGAGCUUAUUCGAAA NM_020886 3166 USP28 GGCAAUACAUGUUGGUUUA NM_020886 3167 USP28 GGAACAGUUUGCAGAUAAA NM_020886 3168 USP28 GAAGGUGGCUCAAGCGAAA NM_020886 3169 USP28 GAAAUAAGAGAGAGUGUAU NM_020886 3170 USP28 CUGUGGAACUCAAGCAUUA NM_020886 3171 USP28 GAAAGUUGAAGGAGGAAAU NM_020886 3172 USP28 GGAAGAAGUUGAAAGAGAU NM_020886 3173 USP28 GGCAGAAAGCAGUGUAUUA NM_020886 3174 USP28 AGUUGAAGGAGGAAAUAAA NM_020886 3175 USP28 GACCAGACAUCCAAGGAAA NM_020886 3176 USP28 ACAAGGAAGUAUUAGCAAA NM_020886 3177 USP28 AGAAGUGGCAUGAAGAUUA NM_020886 3178 USP28 GAGAGAAAUCACAGGCAUU NM_020886 3179 USP28 UGUCGAAGUCAUACAGAAA NM_020886 3180 USP28 CAAGCGAAACUGAAGGAAA NM_020886 3181 USP28 CAGCAAGAUGUGAGUGAAU NM_020886 3182 USP28 UGGAACAGUUUGCAGAUAA NM_020886 3183 USP28 GAUUAUAGUUUGUUCCGAA NM_020886 3184 USP28 UGAAUAUGGAAGAGUACAA NM_020886 3185 USP28 CUAAACGCUCAAAGAGAAA NM_020886 3186 USP28 GGAGUGAGAUUGAACAAGA NM_020886 3187 USP28 AAUUCAAGCUGAUGGAAGA NM_020886 3188 USP28 GCAACUUAGACGAGUGUUU NM_020886 3189 USP29 GUACAAAGAUCAAGAGAGA NM_020903 3190 USP29 GGAAUAUGCUGAAGGAAAU NM_020903 3191 USP29 AGGAAUAUGCUGAAGGAAA NM_020903 3192 USP29 AGACAGAUUCCUUGAAAUA NM_020903 3193 USP29 ACAAAGAUCAAGAGAGAAU NM_020903 3194 USP29 AUACAAAGCAAUAGGAAGA NM_020903 3195 USP29 CCAAGGAACUAACAAGAAA NM_020903 3196 USP29 CAUCAAGUUUAGAGGAUUU NM_020903 3197 USP29 CAUGAAAGUUUGAAGAACA NM_020903 3198 USP29 GGAUGAAAUCUCAAUGAAA NM_020903 3199 USP29 UGAAAGAAGACAUGGAAAA NM_020903 3200 USP29 GAUGAUAUCUCUAAAGGUA NM_020903 3201 USP29 CAAUCAGUCUACAGAAUUA NM_020903 3202 USP29 GGUGAAGAAUAACGAGCAA NM_020903 3203 USP29 GUGCAAAGACAAAAGGAAA NM_020903 3204 USP29 UUGAGGAGCUGUUAAGAAA NM_020903 3205 USP29 GCUAGGGACUGAUUAGAAA NM_020903 3206 USP29 GCUGAAGGAAAUUGACAAA NM_020903 3207 USP29 GAAACAGUGCAAAGACAAA NM_020903 3208 USP29 GGUUGCUGGUGAAGAAUAA NM_020903 3209 USP29 AAGAAGAAGAGCUUGAAUA NM_020903 3210 USP29 UUGUAAAGCUUGUGGUCAU NM_020903 3211 USP29 AGAAGAAGAGCUUGAAUAU NM_020903 3212 USP29 GAGAGAAUUACUUGGGAAU NM_020903 3213 USP29 GUAUGAAGAUGGAGGGAAG NM_020903 3214 USP29 CUUUAAAGAAGAAGAGCUU NM_020903 3215 USP29 CCAGAGAGACUGUGGAGAU NM_020903 3216 USP29 CAGAAGAUGCCUUUGUUUA NM_020903 3217 USP29 CUGAAAGAAGACAUGGAAA NM_020903 3218 USP29 GGAAAAUGGCUCUGCACUA NM_020903 3219 USP3 GUAGAAGAGUUUAGAAAGA NM_006537 3220 USP3 GGAGUUAAGGAAUGGGAAA NM_006537 3221 USP3 GUGAUGAUUUUGUGGUUAA NM_006537 3222 USP3 UGGUAGAAGAGUUUAGAAA NM_006537 3223 USP3 GGACAGCAUAUUUAAGAAA NM_006537 3224 USP3 AGAAGAACUUGAUGAGACA NM_006537 3225 USP3 GGGACAGAAUCUAGAAAGU NM_006537 3226 USP3 CACAAUGACUGCUGAGGAA NM_006537 3227 USP3 UAACAAAGGGCAUCAUUAA NM_006537 3228 USP3 CCAAGUCAGUUCAGAAGUA NM_006537 3229 USP3 CCACAAAAUUUCACAAUGA NM_006537 3230 USP3 GGCCAAAGCUGGAUCGGAU NM_006537 3231 USP3 CUAGAAAGUUUGAUCCAUU NM_006537 3232 USP3 GACAGAAUCUAGAAAGUUU NM_006537 3233 USP3 GAGAACACUUACAGAACUU NM_006537 3234 USP3 GCUCUAAGAAUCAAGAAAA NM_006537 3235 USP3 ACUCAACACUAAACAGCAA NM_006537 3236 USP3 GGCUAUAUUCGGAGGCAUU NM_006537 3237 USP3 AGACUGUGGUGAAGGCGAA NM_006537 3238 USP3 CCAUGAAUUCAAUGCGCUA NM_006537 3239 USP3 GGGAUAACAAUGUGUCUUU NM_006537 3240 USP3 AGAAGAGUUUAGAAAGACA NM_006537 3241 USP3 UUGCAUAAAUGGAGCAUCU NM_006537 3242 USP3 ACGAGGAGACUGUGGUGAA NM_006537 3243 USP3 GUACAGAAAGUCAGAGAAC NM_006537 3244 USP3 UUGAUGAGACAGAGUUAUA NM_006537 3245 USP3 GCUGAAAGCAAGAUGUGUU NM_006537 3246 USP3 ACACUAAACAGCAAGUUAU NM_006537 3247 USP3 CCAAAGCUGGAUCGGAUAA NM_006537 3248 USP3 CGUAGAAUUUCCACUGAGA NM_006537 3249 USP30 GUACAAAGAUUGAAGCCAA NM_032663 3250 USP30 GAAAUAACUCCCAAACAAA NM_032663 3251 USP30 GGGAGUUAUAGGUGGAAUU NM_032663 3252 USP30 CAUUGGAAGAUGAGCGAGA NM_032663 3253 USP30 GGACAUAAACCUAGUCAAC NM_032663 3254 USP30 ACAGAAAGAAAGAAGCGUA NM_032663 3255 USP30 CAUCAGAAUCAGUGCGGGA NM_032663 3256 USP30 GCGCCUACCUGCUGUUCUA NM_032663 3257 USP30 GAACAAGAACCCAGGGCCU NM_032663 3258 USP30 UGAUGGACAUUUACAAGUA NM_032663 3259 USP30 UGUUGGAUGUCUUAAGAAU NM_032663 3260 USP30 AAGAAAGAAGCGUAGAAAA NM_032663 3261 USP30 AGAAAGAAGCGUAGAAAAG NM_032663 3262 USP30 GCCAAGAAGUUACUGAUGA NM_032663 3263 USP31 GGAUAAAGGAAAAGCAAAA NM_032236 3264 USP31 GUGCAAGAUUUUAGAAAGA NM_032236 3265 USP31 CAAAUUUGUUCCAGGAUAA NM_032236 3266 USP31 GGACAAGGAAGAAGCUAAA NM_032236 3267 USP31 GAAGAAGGGUUUAAAGGUA NM_032236 3268 USP31 GAAAAGAAGAGGAGGAAUU NM_032236 3269 USP31 CAGUAAAGGGCGAUGGAUU NM_032236 3270 USP31 GCAGGAUGCUCAAGAAUUU NM_032236 3271 USP31 CCAAAUUUGUUCCAGGAUA NM_032236 3272 USP31 CCAUAAAGUUGUGGAUAAU NM_032236 3273 USP31 GCAAACUGGACAUAAGAAA NM_032236 3274 USP31 GUUUAAAGGUACUGGUCUU NM_032236 3275 USP31 AAGAAGAGGAGGAAUUAAA NM_032236 3276 USP31 CUGAAACAGAGGAGGACAA NM_032236 3277 USP31 GGCGGAAAUUUGUUAGAAA NM_032236 3278 USP31 AGUAGAACGUUGUCGCAUA NM_032236 3279 USP31 ACAGCAAGUCUGAGGACAA NM_020718 3280 USP31 AUGCAAAUACAACGGGAAA NM_020718 3281 USP31 CUUCAAGACUAUUGUGUCA NM_020718 3282 USP31 UGUCAGAAACAGAGCAACA NM_020718 3283 USP31 UCGUAGAUACACAGAGCAA NM_020718 3284 USP31 CAAAGAAACCAGAGAGCAC NM_020718 3285 USP31 UUGUAAAUACUGAGGAUGA NM_020718 3286 USP31 AUUUAGGCCUGAAGGAAUU NM_020718 3287 USP32 AGGCAAAGAUGAAGAGAAA NM_032582 3288 USP32 GGAGAUAUCCUGUGGGUUA NM_032582 3289 USP32 GUAAAUGGUCGGUGGAUAA NM_032582 3290 USP32 GAUCAAUUGUUGUGGAUUU NM_032582 3291 USP32 GGACAAAUUAUUAGAGGAU NM_032582 3292 USP32 GGAAGAAGAAGGACAAAUU NM_032582 3293 USP32 GAAUACUACAGAAGAGAAA NM_032582 3294 USP32 GCAUUAAAGAGGAAGAUAU NM_032582 3295 USP32 CAGCUAAGAUCUCAAGUAA NM_032582 3296 USP32 GCAUAUAAGUGUCCGAUUU NM_032582 3297 USP32 GGACAAAUCCCAUUGGUAU NM_032582 3298 USP32 GUACAUGGUUCCAACAUAA NM_032582 3299 USP32 GAGAAACGCUAUUGGUUAU NM_032582 3300 USP32 AGUAAAGGCUACAUCAUUA NM_032582 3301 USP32 UGGCAAGGGAGGUGAAGAA NM_032582 3302 USP32 UGGCAACAGUGGAAAGAAU NM_032582 3303 USP32 ACUAGAAGGAGGACGAUUA NM_032582 3304 USP32 GAACUAUGUUAUACGGGAA NM_032582 3305 USP32 UCACAAAUGGAAUGGUUAA NM_032582 3306 USP32 UAUCAAACAUCCCAGGAAA NM_032582 3307 USP32 CAGUAUGGAUGAAGACUUU NM_032582 3308 USP32 GGACAACCAUCUAAGAAGA NM_032582 3309 USP32 GUGGAAAGAAUAUGUCAAA NM_032582 3310 USP32 UGAUAUUGUAGAAGGCAUA NM_032582 3311 USP32 AUGCAGACCAUCAAGGAAA NM_032582 3312 USP32 ACGAUUUGAUUUAGAGACA NM_032582 3313 USP33 CAGCAGAGCUUCAGAAUAU NM_015017 3314 USP33 UUUUGAAAGUCUUGGGAAA NM_015017 3315 USP33 CAACAGUGAUAGAGCAGAA NM_015017 3316 USP33 AAAGAGAAGAUGUGCAAUA NM_015017 3317 USP33 AGACAAUGGAAGAAGACAA NM_015017 3318 USP33 AGACAUAUUUGAUGGAACA NM_015017 3319 USP33 GGAAAUACUUGUUACAUGA NM_015017 3320 USP33 CAGCUCAAAUUGUGACAUA NM_015017 3321 USP33 UGGAAUAUGUGAAGAGGUU NM_015017 3322 USP33 AGUCAUGGAAGUAGAAGAA NM_015017 3323 USP33 AAAGAGAGGAGAAGGAUAU NM_015017 3324 USP33 UCAGAAAUGUCAAAGGAUU NM_015017 3325 USP33 AGUAAAUUCUGAAGGCGAA NM_015017 3326 USP33 CGACAGUGGCUUAAUAAAU NM_015017 3327 USP33 CUGAAACAGUCGACUUAAA NM_015017 3328 USP33 GGACUAGCUCGAACAGAUA NM_015017 3329 USP33 GGGCAUGUCUGGAGAAUAG NM_015017 3330 USP33 UCAUGGAAGUAGAAGAAGA NM_015017 3331 USP33 GGAGAAGGAUAUCAAAUUU NM_015017 3332 USP33 UCAUGUUGAUCCAGAUAUA NM_015017 3333 USP33 UGGAAGAAGACAAGAGCCA NM_201624 3334 USP33 AUAUAGAAGCGGAUGAAGA NM_015017 3335 USP33 GGAAACUGUCAAAGUGCAA NM_201624 3336 USP33 GAUCAUGUGGCGAAGCAUA NM_015017 3337 USP33 CAAUGUUAAUUCAGGAUGA NM_015017 3338 USP34 GGAUAUAGUCCAAGAUGAA NM_014709 3339 USP34 GCGGAAAGCCAUAGGAAAA NM_014709 3340 USP34 CUACAAAGCUAGUGCCCUA NM_014709 3341 USP34 CAGGUUAAGUUUAGAGCAA NM_014709 3342 USP34 AUAGAAAGUUAGAGAGUCA NM_014709 3343 USP34 GGGAAGAAGAAGAGGAGGA NM_014709 3344 USP34 GGGCAUGUUUUAAGAAAUU NM_014709 3345 USP34 CAAGCUAAUAGGAGGGAAA NM_014709 3346 USP34 GCAUGGAACCAGAGGAAGA NM_014709 3347 USP34 GGUUCAAAGUCAAGUGUUU NM_014709 3348 USP34 GGGAAAGAGUGAGAGGAAA NM_014709 3349 USP34 GAAGAAAGUACGAGCUGAA NM_014709 3350 USP34 CGGAAUAGAAAGUUAGAGA NM_014709 3351 USP34 GAGCAAGAAGCCAAAGAAA NM_014709 3352 USP34 CCUAAUAUGUUGAUGGCAU NM_014709 3353 USP34 GCAUAUAAUCCUAGACCUU NM_014709 3354 USP34 GGAUAUGGGAGGUGAUUGA NM_014709 3355 USP34 UGGGAAAGAGUGAGAGGAA NM_014709 3356 USP34 GAGAAGAAGAAUUAGAAGA NM_014709 3357 USP34 AUUAAAGCACUGUGGAAUA NM_014709 3358 USP34 CAUAUUUAAUGGAGAGUGA NM_014709 3359 USP34 GAACCAAACAUGUGCAACA NM_014709 3360 USP34 AGAUAUGAGAGAAGAAGAA NM_014709 3361 USP34 CAAAAGACUCAGAGAGCUA NM_014709 3362 USP34 CAGAAAGGCAUUUGACAUU NM_014709 3363 USP34 GAGCUUACGAUGUGAAGAA NM_014709 3364 USP34 CAUCUGAGACAGUGGCAAA NM_014709 3365 USP34 CCAAGUAUUCAGAGGAUAU NM_014709 3366 USP34 GGAAAGAGUGAGAGGAAAG NM_014709 3367 USP34 UCUCAUGGUUAUAGAAAGA NM_014709 3368 USP35 GGAUAGAGAGGGAGGAAGA XM_290527 3369 USP35 AAGAAGAGAAGGUGGAGAA XM_290527 3370 USP35 AGGAAAGGAUAGAGAGGGA XM_290527 3371 USP35 GUGGAGAAGGAGACAGAAA XM_290527 3372 USP35 UGGAAGAGGAAGAAGAGAA XM_290527 3373 USP35 AAGAGAAGGUGGAGAAGGA XM_290527 3374 USP35 AAGACAAGGAUGAGGAUGA XM_290527 3375 USP35 GGAAGGAGAGAGGGAGAAA XM_290527 3376 USP35 AGAAAGAGGAGGAGGUGGA XM_290527 3377 USP35 GGAAAGCACCAGAGGGGAA XM_290527 3378 USP35 GUUAAGAAGUUCAGCAUCU XM_290527 3379 USP35 GGGAGAAAGAGGAGGAGGU XM_290527 3380 USP35 AAGGAGAGAGGGAGAAAGA XM_290527 3381 USP35 CCGAGAAGGUGGUGGAGCU XM_290527 3382 USP35 AAGAGGAGGAGGUGGAAGA XM_290527 3383 USP35 GCUCGGAGUAUCUGAAGUA XM_290527 3384 USP35 AGAGCGAGCUGGCGGGUUU XM_290527 3385 USP35 AGGAAGAAGGGAAGGAGGA XM_290527 3386 USP35 GGAGGAGGUGGAAGAGGAA XM_290527 3387 USP35 AGGAGGAGGUGGAAGAGGA XM_290527 3388 USP35 AGAGGGAGGAAGAAGGGAA XM_290527 3389 USP35 AGGAAGAAGAGAAGGUGGA XM_290527 3390 USP35 AGGAGGUGGAAGAGGAAGA XM_290527 3391 USP35 AGACAAGGAUGAGGAUGAA XM_290527 3392 USP35 GGAAGAGGAAGAAGAGAAG XM_290527 3393 USP35 AGAGAACGGAGAAGGAAGA XM_290527 3394 USP35 GAGAAGGUGGAGAAGGAGA XM_290527 3395 USP35 AGACAGAAAAGGAGGCUGA XM_290527 3396 USP35 AGGUGGAGAAGGAGACAGA XM_290527 3397 USP35 AGGUGGAAGAGGAAGAAGA XM_290527 3398 USP36 GGGAAGAGGAAGAGGAAGA NM_025090 3399 USP36 GGAAGAGUCUCCAAGGAAA NM_025090 3400 USP36 UGAUAAAGCUUACGGGAGA NM_025090 3401 USP36 CGUAUAUGUCCCAGAAUAA NM_025090 3402 USP36 GGAAGAGGAAGAAGAAGAA NM_025090 3403 USP36 CUGGAAAGAAGGUGAAGAA NM_025090 3404 USP36 AGGAAGAGGAAGAAGAAGA NM_025090 3405 USP36 AAAGAAAGCAGGAGACACA NM_025090 3406 USP36 GGACUGAGACCGUGGUUGA NM_025090 3407 USP36 GCACACCACUGAAGAGAUU NM_025090 3408 USP36 UGUCCUGAGUGGAGAGAAU NM_025090 3409 USP36 GUGCUAAAUGCAAGAAGAA NM_025090 3410 USP36 AAGAGAGAGAAGAGGAGAA NM_025090 3411 USP36 GGGAAGGAAAAGAAAAUUA NM_025090 3412 USP36 AGAGAGAAGAGGAGAAACU NM_025090 3413 USP36 CCAAGAAGAACAUCGGCAA NM_025090 3414 USP36 GGAAAGGAGCAGAAGGUCU NM_025090 3415 USP36 GGACAGUGGUACCAGAUGA NM_025090 3416 USP36 CACCAAGGAUGUAGGCUAU NM_025090 3417 USP36 GAAAGGAGCAGAAGGUCUU NM_025090 3418 USP36 AGCAGAAGGUCUUGGUGAA NM_025090 3419 USP36 UCACCAAGGAUGUAGGCUA NM_025090 3420 USP36 AGAGAGAGAAGAGGAGAAA NM_025090 3421 USP36 AGAGGAAGAGGAAGAAGAA NM_025090 3422 USP36 GAGGAGGAAAGGAGCAGAA NM_025090 3423 USP36 CGACAAGACUCUGGGACGA NM_025090 3424 USP36 CUCAAAUACUCAUCUGAUA NM_025090 3425 USP37 CUACAAUACUGGAGGAAUU NM_020935 3426 USP37 GAAGAUUACCCUAAGGAAA NM_020935 3427 USP37 CAAAAGAGCUACCGAGUUA NM_020935 3428 USP37 GAAAAGAAAUGCUGAGACA NM_020935 3429 USP37 GCUCAGAAUUGAAUGAAGA NM_020935 3430 USP37 AAGUAAGGAUGCAGAGGAA NM_020935 3431 USP37 GCGUGAAAGGGAAGAGCAA NM_020935 3432 USP37 GUGAAAGGGAAGAGCAAGA NM_020935 3433 USP37 GUAAGGAUGCAGAGGAAAU NM_020935 3434 USP37 GGAAAUACCUGCUAUAUGA NM_020935 3435 USP37 CCGAAGAACUGGAGUAUUC NM_020935 3436 USP37 GAAAAGAGGAAAAGAAUGA NM_020935 3437 USP37 GAGAAAAGCAGCUGAGUUU NM_020935 3438 USP37 CUGAAAGAAGAUAUGGAAA NM_020935 3439 USP37 GAUUAAGACUGUAGCAGGA NM_020935 3440 USP37 UCGAAAAGUUCUUGGUAAU NM_020935 3441 USP37 CAGCUAAGUCAUAACAUUA NM_020935 3442 USP37 GAAGAAAAUUCACCAGAUA NM_020935 3443 USP37 ACUCAGGAUUUGACAGAAU NM_020935 3444 USP37 AGAUCAGGGUUGCUAGAAA NM_020935 3445 USP37 GAAACAGUCAGAAGAGAAU NM_020935 3446 USP37 GGGCCGAAGAACUGGAGUA NM_020935 3447 USP37 UGACAGAAUGAGCGAAGAA NM_020935 3448 USP37 AGCCAGAGACUUUGUGAAA NM_020935 3449 USP37 GAGAUAAGUAAGAGAGAUG NM_020935 3450 USP37 GGGAACAGAAAGAAGAUGA NM_020935 3451 USP37 CUGAGGAACUGAAAAGAAA NM_020935 3452 USP37 GGAGGAAUUCCAAGGAUAU NM_020935 3453 USP37 UGUAGCAGGAAGUGGAAUA NM_020935 3454 USP37 GAAUAGGACAUCAGGGCUU NM_020935 3455 USP38 GCAUAGUACUAAUGGUUUA NM_032557 3456 USP38 CAGAAGAACCAGUAGUUUA NM_032557 3457 USP38 ACACAAGCCUUCUGAAAUU NM_032557 3458 USP38 GGAAGUAGCUAGUAAAGCA NM_032557 3459 USP38 GAAAGAGAGCUGCGGGAAU NM_032557 3460 USP38 CAGCAAGACUGUUCUGAAU NM_032557 3461 USP38 ACUAAUGGUUUAAGUGGUA NM_032557 3462 USP38 UCAGAAACCAGGAGGUGAA NM_032557 3463 USP38 GGUAAUUGCACUCCUGAAA NM_032557 3464 USP38 GUAACUUGCUGCAGAACAU NM_032557 3465 USP38 GAGUUUUACUGUUCUGAAA NM_032557 3466 USP38 CUGGAUAAAUGGAGACCCA NM_032557 3467 USP38 GUAUCAUGUGAGAAGGAAA NM_032557 3468 USP38 UUUAAUGACAGUAGAGUGA NM_032557 3469 USP38 AGGUAGAGGUGUUACGGAU NM_032557 3470 USP39 UGAAUAACAUAAAGGCCAA NM_006590 3471 USP39 GAGAAUACUUGUCUGAAGA NM_006590 3472 USP39 CCAUGAGGAUCUUCACUAA NM_006590 3473 USP39 GCAUCACUGAGAAGGAAUA NM_006590 3474 USP39 ACGAGUACCAGGAGACAAU NM_006590 3475 USP39 CAAAUGUGGAUCUGAGAGA NM_006590 3476 USP39 UCACUGAGAAGGAAUAUAA NM_006590 3477 USP39 AGACUUACAAGGAGAACUU NM_006590 3478 USP39 CUGAAUAACAUAAAGGCCA NM_006590 3479 USP39 GGGUAUUGUGGGACUGAAU NM_006590 3480 USP39 UGGCUAAGUUCAAUGGCAU NM_006590 3481 USP39 UCUUCAACAUCCUGGCUAA NM_006590 3482 USP4 CCAAAUGGAUGAAGGUUUA NM_003363 3483 USP4 AGAACAAACUGAAUGGUAA NM_003363 3484 USP4 GAACAAACUGAAUGGUAAA NM_003363 3485 USP4 GGAACAAAUACAUGAGCAA NM_199443 3486 USP4 AGGAAGAAAUGGAGCAUCA NM_003363 3487 USP4 GGAAGAAGUAUGUGGGCUU NM_003363 3488 USP4 GAGAAGAUGAGGAAGAAAU NM_003363 3489 USP4 CUGCAUAUGCGAAGAACAA NM_003363 3490 USP4 CCUCAGAAGAAGAAGAAGA NM_003363 3491 USP4 AACAGAUACUGGAGGGAUA NM_003363 3492 USP4 GCAAAUGGUGAUAGCACUA NM_003363 3493 USP4 GGGAAGAUGAGCCAGGAAA NM_003363 3494 USP4 CCUACGAGCAGUUGAGCAA NM_003363 3495 USP4 GAACAGCUGUGAAGGAGAA NM_003363 3496 USP4 GGAAAUUGCAGAAGCCUAU NM_003363 3497 USP4 GGAAGAUGAGCCAGGAAAU NM_003363 3498 USP4 AAGGAGAAGAUGAGGAAGA NM_199443 3499 USP4 GGGAUAAGCUCGACACAGU NM_003363 3500 USP4 GCAUCAGGAAGAAGGCAAA NM_003363 3501 USP4 GGGAAAUUGCAGAAGCCUA NM_199443 3502 USP4 ACGAGAAGCAUGUGAGCAU NM_003363 3503 USP4 CAGAUGCGGUGGUGGCAAA NM_003363 3504 USP4 GAGAGGAAGUCCAGGCCAU NM_003363 3505 USP4 GCAAAGUCGAGGUGUAUUU NM_003363 3506 USP4 GAAGAAAGAUCGAGUUAUG NM_003363 3507 USP4 ACUGCAAAGUCGAGGUGUA NM_003363 3508 USP4 GCAAAGGAAGCCUGGGAGA NM_003363 3509 USP4 GAACUGAAGCUCUGUGAGA NM_003363 3510 USP4 UGAAGGAGAAGAUGAGGAA NM_003363 3511 USP4 CAGAAGAAGAAGAAGACCA NM_199443 3512 USP40 GGGAAGAAAUUAAAGACUA NM_018218 3513 USP40 GCUUUUAAUUGAAGGACAA NM_018218 3514 USP40 CAAAUAACCAAGAGGAAAA NM_018218 3515 USP40 GGAAAAGGGAAGAAAUUAA NM_018218 3516 USP40 AAACAAUAUCUGUGAGAGA NM_018218 3517 USP40 AGGAUAAACCCGAUGCAAA NM_018218 3518 USP40 CCAAGGAAGACAUGAGGAA NM_018218 3519 USP40 CAAUCUUAUUAGAGGAGAA NM_018218 3520 USP40 GCUCAGAAAUGGAAGCUCA NM_018218 3521 USP40 AGUUAGAAUCUGAAGAGAA NM_018218 3522 USP40 ACAAAUAACCAAGAGGAAA NM_018218 3523 USP40 GGACCAGUAAUGAGGAAAU NM_018218 3524 USP40 CUGAAGAGAAGCAAGUUAA NM_018218 3525 USP40 CCAGAGUGAAGAAGAGAUU NM_018218 3526 USP40 AAGGAAGACAUGAGGAAGA NM_018218 3527 USP40 UGAAAUUGCUGAUGGGGAA NM_018218 3528 USP40 UGUAAGAACGUUAGCGAGA NM_018218 3529 USP40 UGGAAAUCGUAGUAGAAGA NM_018218 3530 USP40 CUAUGAAGCUGGAGAGCCU NM_018218 3531 USP40 GGGACUGUGUCUUGGAAAA NM_018218 3532 USP40 AAGUAAACCAGAUGUGAAU NM_018218 3533 USP40 CCUGGACGGUGGAGAGGAA NM_018218 3534 USP40 GGAUUAAUCUCAAGCCCUU NM_018218 3535 USP40 CUGAUAUGUUCUGGAGAUA NM_018218 3536 USP40 GCAGAAUUGAAGAUGGGAA NM_018218 3537 USP40 AGUUAAUGCUGAAGAAAUC NM_018218 3538 USP40 AAUCAUCCCUUUACAGUUA NM_018218 3539 USP40 GGGAAAAGGAUAUUGAACA NM_018218 3540 USP40 AUGUUGAUCAUUUGGGAAA NM_018218 3541 USP40 CGGAGAUACUAUUGGUGUU NM_018218 3542 USP42 CGGAACAGCUUGAUGGAGA XM_374396 3543 USP42 GGGCAAGGAGAAUGGGAUU XM_374396 3544 USP42 CUAGAAGAGCCUAAAGCAA XM_374396 3545 USP42 UCUGAAACGUUUUGCAAAU XM_376571 3546 USP42 GGAGCAAGACUGAGGGCCA XM_374396 3547 USP42 CAGCAAUAAAUUAGACAGA XM_376571 3548 USP42 CAUAGUAAUUCUUUGGAGA XM_376571 3549 USP42 CAAGAAAAUCAGAGGACUU XM_376571 3550 USP42 AGUCAAAGGGGCUGGGCAA XM_374396 3551 USP42 CUGAAAGGCUCGACGGAUG XM_374396 3552 USP42 GCUUCAAAGAGGUUCACUA XM_374396 3553 USP42 CAGUCAUGUUGAAAAGAAA XM_374396 3554 USP42 CUUGAAUGGCAGCAAUAAA XM_374396 3555 USP42 GCUCCCAGCCCGUGAUGAA XM_374396 3556 USP42 CAGUGAUAUUAGAUCGGUA XM_374396 3557 USP42 CCAAAGACAAACACCGAGA XM_374396 3558 USP42 GUGCAGACAGCGACAGUGA XM_374396 3559 USP42 ACAAAAGGAUCAAGCCCUA XM_374396 3560 USP42 CUCCAGAAUUUGGGCAAUA XM_376571 3561 USP42 GCAACAAACUGAAAGGCUC XM_376571 3562 USP42 CCUGGAACGUACAGCUCUA XM_376571 3563 USP42 GCUUAGCAACAAACUGAAA XM_374396 3564 USP42 UCAACAAGGCAUUGGAGCA XM_374396 3565 USP42 CUUCAGGCUUAGCAACAAA XM_374396 3566 USP42 GGCCAUUACUUCUGCUACA XM_374396 3567 USP42 AAACACUUACGGAUGGAAA XM_376571 3568 USP42 CUAAAGCAAAGAAGCACAA XM_376571 3569 USP42 GGAAAGUCCCGGAAACGGA XM_374396 3570 USP42 CACUCUUGUUUGUCAGAUA XM_374396 3571 USP42 CAGUCUACCUCGAACGCAU XM_374396 3572 USP43 GCCAUGAACUGGAAGGAGA XM_371015 3573 USP43 GCUUGAAGAACCACGGCAA XM_371015 3574 USP43 GCUCUCAGUUCCAAGGCAA XM_371015 3575 USP43 AGACGAGGUUCUUGAGUGU XM_371015 3576 USP43 GCGCUCAGGGCUUGAAGAA XM_371015 3577 USP43 GGAAGAUGGUUGCAGAGGA XM_371015 3578 USP43 CGGAAGAAGGAGAACAGGA XM_371015 3579 USP43 GAGAUAAUGUGUAUGCCUU XM_371015 3580 USP43 GUGCAGUGUCUCAGCAACA XM_371015 3581 USP43 CAGCAAAGACAGUCGCCGA XM_371015 3582 USP43 AUACCAUCGCAGAGGGAGA XM_371015 3583 USP43 UGAACUGGAAGGAGAGCUU XM_371015 3584 USP43 GAGGAUGAGAAGUCAGCAU XM_371015 3585 USP43 CAGGUGGGCGAGAGAAGAA XM_371015 3586 USP44 GUAACAGGAUUGAGAAAUU NM_032147 3587 USP44 AAGCAGAAUUGGAAAGUAU NM_032147 3588 USP44 GAUUGAGAAAUUUGGGAAA NM_032147 3589 USP44 GUAUCAAGUUAAAGCAGAA NM_032147 3590 USP44 GUGUAACAGGAUUGAGAAA NM_032147 3591 USP44 GGAAAUACUUGCUAUAUGA NM_032147 3592 USP44 AAACUAAGCAUGUGCACUA NM_032147 3593 USP44 ACUAAGUGGUGGAGCAUCA NM_032147 3594 USP44 UCUUAAACAUGGAGCCCUA NM_032147 3595 USP44 AUGAAUGAAUGUCAGGAAA NM_032147 3596 USP44 CUGAAGCUUUAGAAGGAAA NM_032147 3597 USP44 GGUAAAAUCUUUCGAACAU NM_032147 3598 USP44 GAAUUGGAGUAUCAAGUUA NM_032147 3599 USP44 CUGAAAUGUUGGCCAAAUU NM_032147 3600 USP44 GCUCUUUGGCACAGGAGAA NM_032147 3601 USP44 CCAUGUUGCCUGUGGAAGA NM_032147 3602 USP44 GGACGUAAUAACCGAGAGA NM_032147 3603 USP46 CAGAAAAGGAUGAGGGUAA NM_022832 3604 USP46 CAGCAAAAGAAGAAGGAAA NM_022832 3605 USP46 UGAUGACAUUGUAGAGAAA NM_022832 3606 USP46 CCAAAGAAGUUCAUUUCAA NM_022832 3607 USP46 CUAUCAGUCAAGAGAGUAA NM_022832 3608 USP46 GAGGAGAAGAAACAGGAAA NM_022832 3609 USP46 AGCAAAAGAAGAAGGAAAA NM_022832 3610 USP46 GGUCAAUUUUGGAAACACA NM_022832 3611 USP46 AGGAGAAGAAACAGGAAAA NM_022832 3612 USP46 CUAAGAGACUUCAGCAACA NM_022832 3613 USP46 CAUACAAGGCCCAGCAAAA NM_022832 3614 USP47 GAACAGAAAUGGAAGCAAA NM_017944 3615 USP47 GAAAGCAAAUGAAGGGAAA NM_017944 3616 USP47 CCUGAAAGCUGAAGGAUUU NM_017944 3617 USP47 GCGCAAUACAUGCAAGAUA NM_017944 3618 USP47 GCUUAUAAGAUGAUGGAUU NM_017944 3619 USP47 AGGAAUGACUGUACGGCAA NM_017944 3620 USP47 CAGCAAAAGUACUGAGACA NM_017944 3621 USP47 GAAAAGAGACAACGAGAAA NM_017944 3622 USP47 GGAUAUUAUUCUAGUGCUU NM_017944 3623 USP47 GCUCCGAGACUUUGGAUUA NM_017944 3624 USP47 CGCAAUACAUGCAAGAUAA NM_017944 3625 USP47 UGACAGAUGAGCAAAGAAA NM_017944 3626 USP47 GUGAAUAAUGACAGGAGUA NM_017944 3627 USP47 GGAUAACACAAGAGGACAU NM_017944 3628 USP47 AGAGAGAGUUGGAAGAACA NM_017944 3629 USP47 GCAUUAUAUAAGUGGGAAU NM_017944 3630 USP47 GGAUGAUGACUGUGAAAGA NM_017944 3631 USP47 AAGGCAAGCUGAAGGACUA NM_017944 3632 USP47 AAAGGAGAAUACAGAGUUA NM_017944 3633 USP47 AGUAGAAGAACGAAAGCAA NM_017944 3634 USP47 GUAUAAAGUCAUUCAGUGA NM_017944 3635 USP49 GGGCAAGAGUGUUCAGCAA NM_004275 3636 USP49 GAGAAUGGCCCUUGCCUUA NM_004275 3637 USP49 GGGCAGAGAAGCAAGGAAC NM_004275 3638 USP49 GUGUGGACUGUGAGACUUA NM_004275 3639 USP49 UCGAGUUCCUACAGAGUUU NM_004275 3640 USP49 GGCAAGAGUGUUCAGCAAA NM_004275 3641 USP5 CCACAGAGAAGGUGAAGUA NM_003481 3642 USP5 UGGAUAAGCUGGAGAAGAU NM_003481 3643 USP5 UCAACAUGGUGGAGAGGAA NM_003481 3644 USP5 AGAGGAAGUAUGUGGAUAA NM_003481 3645 USP5 UGACUGAGUUGGAGAUAGA NM_003481 3646 USP5 AAGAGGAGCUUCUGGAGUA NM_003481 3647 USP5 GAGCAGAGGGGCAGCGAUA NM_003481 3648 USP5 GGAUGGUCCUGGAAAGUAU NM_003481 3649 USP5 UGGAGUACGAGGAGAAGAA NM_003481 3650 USP5 CGAGGAGAAGUUUGAAUUA NM_003481 3651 USP5 GGAUGCAGCCCUUAACAAA NM_003481 3652 USP5 AGAGAGAACCUGUGGCUCA NM_003481 3653 USP5 AGGAGAAGUUUGAAUUAGA NM_003481 3654 USP5 GAGCUGACGUGUACUCAUA NM_003481 3655 USP5 CAGAGGAAGUAUGUGGAUA NM_003481 3656 USP5 GCCUCAAGCAGUUGGACAA NM_003481 3657 USP5 GUGGAGAGACAUUUCAAUA NM_003481 3658 USP5 CAUCAAGAAAGAAGGCAGA NM_003481 3659 USP5 AAAGAAGGCAGAUGGGUGA NM_003481 3660 USP5 GCGAGGAGAAGUUUGAAUU NM_003481 3661 USP5 UGGAGAGACAUUUCAAUAA NM_003481 3662 USP5 AACAGUAUGUGGAGAGACA NM_003481 3663 USP5 CAAAAUACACGAUGUGAAU NM_003481 3664 USP5 CAGACAAGACGAUGACUGA NM_003481 3665 USP5 AAGUGUGACAUGAGAGAGA NM_003481 3666 USP5 AGUUGGAGAUAGACAUGAA NM_003481 3667 USP5 AAGCCGAAGAGGAGAAGAU NM_003481 3668 USP5 GAUCUACAAUGACCAGAAA NM_003481 3669 USP5 CCAAGUGUGACAUGAGAGA NM_003481 3670 USP5 GCUUCUUGGUGGAGGAAAG NM_003481 3671 USP52 GCAGAAAGAUGGACUGGAA NM_014871 3672 USP52 GGGAAAUCUCCAAGAACAA NM_014871 3673 USP52 GAGUCAAGUUUGUGGGUCA NM_014871 3674 USP52 UGGAAAUACCACAGGCUUA NM_014871 3675 USP52 CCAUUGAGGAGUUGAAGAA NM_014871 3676 USP52 AGAACAACCUCAAGUAUAU NM_014871 3677 USP52 UGGAUGAGAAUGAGGAUAU NM_014871 3678 USP52 GCACGGAAGCAGCGGAAAA NM_014871 3679 USP52 CCAUGAAGAAGGUGGGCUU NM_014871 3680 USP52 CCUUCAAGAUGGCAGUAAA NM_014871 3681 USP52 GCACUGAGCCUGAGUCUUU NM_014871 3682 USP52 CAUCAAAGUUGGAGAGACC NM_014871 3683 USP52 GUGUAUGACCUGAUGGCUA NM_014871 3684 USP52 GGGUCUGGAUGCUGAGUUU NM_014871 3685 USP52 GGGAAACCCAUGACAGUAU NM_014871 3686 USP53 CCUAAGAACUGUUGGGUUA XM_052597 3687 USP53 GCAAUGAGGUUGAAAGAAU XM_052597 3688 USP53 GGAAGAGAGUGAACAGUAA XM_052597 3689 USP53 CAGCAUAGUCCAAGACAUA XM_052597 3690 USP53 CAGGCAAAGCAGAGAGAAA XM_052597 3691 USP53 GAUUGGAACUAGAUGGAAA XM_052597 3692 USP53 CGACGAAGCUUGCGGGUUU XM_052597 3693 USP53 GGAUAUCAGUGGUGUUAAA XM_052597 3694 USP53 UGGAAAAGGAGCAGAGAAA XM_052597 3695 USP53 AGCCAAGAUUCUAGGGAUA XM_052597 3696 USP53 GAUAAUUGGCAGAUGCAAA XM_052597 3697 USP53 ACAGAUGACUAUAGGAAAU XM_052597 3698 USP53 CCAUAAUGCAAGAGAACAU XM_052597 3699 USP53 GUUGAAAGAAUGUUGGAAA XM_052597 3700 USP53 GUUAAAUGAACCAGGACAA XM_052597 3701 USP53 UGGAAACCUAUGAGAGAAA XM_052597 3702 USP53 UUACAGAAUUUGUGCGGUA XM_052597 3703 USP53 GGAAAGAUGUUGUCUCCAA XM_052597 3704 USP53 GGGAAGAGAGUGAACAGUA XM_052597 3705 USP53 ACGGAAACCUGGUGGCAAU XM_052597 3706 USP53 GAUGAAAUGAAGCAGGAAA XM_052597 3707 USP53 CGACAAGCAACCUAAAUAA XM_052597 3708 USP53 GGGACAAAGAAAAGAUUUA XM_052597 3709 USP53 UGAAGACAAUGGAAAGUUA XM_052597 3710 USP53 GAUCAAAGGGAAAAGAUAA XM_052597 3711 USP53 GCAUAGUCCAAGACAUAAA XM_052597 3712 USP53 UGACAAUGGCACUGGAUAU XM_052597 3713 USP53 CAACAGAUGACUAUAGGAA XM_052597 3714 USP53 GGGAAAAGAUAAAAGACAU XM_052597 3715 USP53 UCACAUUGAUCAAAGGGAA XM_052597 3716 USP54 ACAAGAAGGAAGAGGCAUU NM_152586 3717 USP54 AGGAAGAGGCAUUGCUCAA NM_152586 3718 USP54 CUCACAGGGUCAAGAGAAA NM_152586 3719 USP54 GGACAGAGGCAGUGAGGAG NM_152586 3720 USP54 CCACAAGAAGGAAGAGGCA NM_152586 3721 USP54 AGUACAGUGCAGAGAAUUU NM_152586 3722 USP54 CAAUAGACUCCCAGGAACU NM_152586 3723 USP54 GGCCAUGGGCAAAGCAACA NM_152586 3724 USP54 GGUGUCUCCAUGAGGGAUA NM_152586 3725 USP54 GUGAGAGAUGUUAGGUCUA NM_152586 3726 USP54 AUUCAUCAAACGUGAGGAA NM_152586 3727 USP54 AGAGAGCAGAUCAGGGCUA NM_152586 3728 USP6 AGGAAAGGGUUGUAGAUAA NM_004505 3729 USP6 GUAAAUGAUCAGUGGAUAA NM_004505 3730 USP6 GCUAAGAUCUCAAGUCAAA NM_004505 3731 USP6 GCGGAGAGGUUCACAACAA NM_004505 3732 USP6 GGAUGGAAAUGCUGGGAGA NM_004505 3733 USP6 CGAAGAAACUAACAAGGAA NM_004505 3734 USP6 GAACAAAUAUGUAGUGAGU NM_004505 3735 USP6 GUACAUGAUUCCAACAUAA NM_004505 3736 USP6 CAAGAGAGGUGAAGAAAGU NM_004505 3737 USP6 GGAGAAUGGGAGACAUAUA NM_004505 3738 USP6 GCACAGGAGCGGAAGGACA NM_004505 3739 USP6 GGAGAAAGCAAGAUCAUGA NM_004505 3740 USP6 GGGCAGUUGUGGAAAGUGA NM_004505 3741 USP6 GGAUGGACAUGGUAGAGAA NM_004505 3742 USP6 ACGAGCAAGUGGAUGGAAA NM_004505 3743 USP6 UGGGAGAAUGGGAGACAUA NM_004505 3744 USP6 CCAUUAGCCUGUAAACAAA NM_004505 3745 USP6 GGAAAGGGUUGUAGAUAAG NM_004505 3746 USP6 GCUAAAUGCUAUGGUGAUU NM_004505 3747 USP6 GGACCUACCCAAACCAAUA NM_004505 3748 USP6 GCUCUAAGGGCUAUAAAUU NM_004505 3749 USP6 CAACAAAGAAGCUGGAUCU NM_004505 3750 USP6 GUCCAGAUAUGAACAAAUA NM_004505 3751 USP6 GCACAGUAGCAAACUCAUA NM_004505 3752 USP6 AGACAGCACUGAUGACCAA NM_004505 3753 USP6 CCAUGUGGCAUCAGGACAA NM_004505 3754 USP7 GGAGAAAGCAUCAGGGAAA NM_003470 3755 USP7 GGACAUAGACAAAGAGAAU NM_003470 3756 USP7 UGAUAAACCUGUAGGAACA NM_003470 3757 USP7 GCGAUUACAAGAAGAGAAA NM_003470 3758 USP7 GAGAAGUGAUGAAGCGAAU NM_003470 3759 USP7 UGAUAAAGCCCUUGAUGAA NM_003470 3760 USP7 CGAAUUUAACAGAGAGAAU NM_003470 3761 USP7 GGUUCAUAGUGGAGAUAAU NM_003470 3762 USP7 CAGAGAAAGGUGUGAAAUU NM_003470 3763 USP7 GUGUAAAGAAGUAGACUAU NM_003470 3764 USP7 CAGAGAGAAUUCAGGACUA NM_003470 3765 USP7 GGGCAUAUCUACACACCAA NM_003470 3766 USP7 AGAAGGAGUUUGAGAAGUU NM_003470 3767 USP7 GAGAACAGGCGAAGUUUUA NM_003470 3768 USP7 CAGCAAUGUUAGAUAAUGA NM_003470 3769 USP7 GAAUUACAGCAUAGUGAUA NM_003470 3770 USP7 GGUAAUCCUCUUAGACAUA NM_003470 3771 USP7 AAACUUAGGCUGCUAGAAA NM_003470 3772 USP7 ACAUAAAUGAAGACGAGUA NM_003470 3773 USP7 ACAUAGACAAAGAGAAUGA NM_003470 3774 USP7 AGAUAAUCAUGGUGGACAU NM_003470 3775 USP7 CUACAACUGAUGAGAUUUA NM_003470 3776 USP7 CUUACAGGAAGCAGAGAAA NM_003470 3777 USP7 GGAAAUAACACUAUAUCCA NM_003470 3778 USP7 AGGAGGACAUGGAGGAUGA NM_003470 3779 USP7 GGGAGAAAGCAUCAGGGAA NM_003470 3780 USP7 GGAACAUGGCUUACAGGAA NM_003470 3781 USP7 GUGCAUCUGUUAAGGCAAA NM_003470 3782 USP7 CCAAUUUAGGGAAGAGGAA NM_003470 3783 USP7 UGACGUGUCUCUUGAUAAA NM_003470 3784 USP8 AAGAAGAAAUGGAGAAGAA NM_005154 3785 USP8 CGAAAGAAAUAAAGCUCAA NM_005154 3786 USP8 GGACAGGACAGUAUAGAUA NM_005154 3787 USP8 CCUGAAGAGCAUAGAAUAA NM_005154 3788 USP8 CUUUAAAGCUGCAGAACAU NM_005154 3789 USP8 AAAUAAAGCUCAACGAGAA NM_005154 3790 USP8 ACACAAUGAUGACGGAUAA NM_005154 3791 USP8 GAAAUGGAGAAGAAAGAAA NM_005154 3792 USP8 GAUAAUCGGAAGAGAUAUA NM_005154 3793 USP8 GUACAAACCAUGAGCAACA NM_005154 3794 USP8 GGAAACAGGAAGAGAGGAU NM_005154 3795 USP8 AGAAAGAGAAACUGAGGAA NM_005154 3796 USP8 GAAACAAGAAGCUGAAGAA NM_005154 3797 USP8 GAAGGAAGAACAAGAACAA NM_005154 3798 USP8 GCAAAGAGGGGCAAAGAAA NM_005154 3799 USP8 GGAAAGGGCCUAUGUACUA NM_005154 3800 USP8 CAAAGAAAUAACAGGAGUA NM_005154 3801 USP8 CCAAGAAAGAAGAUAAAGA NM_005154 3802 USP8 CUGAUAAUCGGAAGAGAUA NM_005154 3803 USP8 AGAAGUUAAACCAGAGAAA NM_005154 3804 USP8 ACAAGAAGCUGAAGAAAAU NM_005154 3805 USP8 GCAAUGAGCCUUUGGUUUU NM_005154 3806 USP8 GUGAACAGGCCAAGAAAGA NM_005154 3807 USP8 GGCCAAGAAAGAAGAUAAA NM_005154 3808 USP8 AGGCCAAGAAAGAAGAUAA NM_005154 3809 USP8 GAGCAAUGGUGAAAAGAAU NM_005154 3810 USP8 GAAGAGAAGAGGAAGCCAA NM_005154 3811 USP8 GAUUAAAGGACAACCAGAA NM_005154 3812 USP8 CAGACGAUACCGAAAGAAA NM_005154 3813 USP8 GGAAAGGCAGCAAGAGGAA NM_005154 3814 USP9X UGAGAGAAGUGUACGGAAA NM_021906 3815 USP9X CCUUAGAGAUGGAGCAAGA NM_004652 3816 USP9X ACAAAUGACAAAUGGGUUA NM_004652 3817 USP9X GGGAUGAUGUAUUUGGAUA NM_004652 3818 USP9X GUGGAGAUGGUGAGAGAAA NM_004652 3819 USP9X GAGAGAAAUCGCUGGUAUA NM_021906 3820 USP9X GAGCACAGCAAGAGAGAGA NM_004652 3821 USP9X GGGUCGUGAUUCAGAGUAA NM_004652 3822 USP9X AGACACAGCUUCUGAAAUU NM_021906 3823 USP9X CCAAGAUGCUCCAGAUGAA NM_004652 3824 USP9X GAACAAGUUAUGUGAAGAA NM_004652 3825 USP9X GGGAUGAGAAGCAGGACAA NM_004652 3826 USP9X CCAAAGGAAUGGUGGAGAU NM_004652 3827 USP9X CAGAAUGGAUACAGCAGAA NM_004652 3828 USP9X GCAAAGGUGUAUAUAGUAU NM_004652 3829 USP9X CCUCAAUGCUCUUAAAAUA NM_004652 3830 USP9X UGACAAAGACAGUGUUAAU NM_004652 3831 USP9X CUGCAGUAAUUCAGAGGAA NM_004652 3832 USP9X ACACGAUGCUUUAGAAUUU NM_021906 3833 USP9X AGGCACAGGUAGUGAUGUA NM_004652 3834 USP9X CAGAAAACCUUGUAACUUA NM_004652 3835 USP9X GGAAUGGCUUGGAGAUGAA NM_004652 3836 USP9X CUAUACAACUAAAGCGAUU NM_021906 3837 USP9X ACGAAUGGCAGAAUGGAUA NM_004652 3838 USP9X AGACUUAGAUCCUGAUAUU NM_004652 3839 USP9X GGACAAGAAGAAACUGUUA NM_004652 3840 USP9X UAUUAAACCAUUUGGGCAA NM_004652 3841 USP9X AGAAAUGGUUCCACAGUUU NM_004652 3842 USP9X GGUGGAUAGUUUAGAUGAA NM_004652 3843 USP9X GAUGAGGCUUCAAGAUAUA NM_021906 3844 USP9Y GGUGGUAACUUUUGAAUUA NM_004654 3845 USP9Y GGAAAGAGAAUGUGCAAUU NM_004654 3846 USP9Y UUUAAGAAGUGGAGAACUA NM_004654 3847 USP9Y ACAAAUGACAAGUGGGUAA NM_004654 3848 USP9Y CAGCAAGAGAGAAGGGUAA NM_004654 3849 USP9Y GAAAUAACUUCUUGCCAAA NM_004654 3850 USP9Y AGGCACAGGUAGUGAUUUA NM_004654 3851 USP9Y UCGAAUGGUUAGAGUAUUA NM_004654 3852 USP9Y GCAAUAAGCUGGAGGUGGA NM_004654 3853 USP9Y GAACUUAGCUUCAAGAAUU NM_004654 3854 USP9Y CCAAAUACAGAUAUGGAAA NM_004654 3855 USP9Y GCGAAUGGCAGAAUGGAUA NM_004654 3856 USP9Y GAGAGAGUGUAGUGAUUAA NM_004654 3857 USP9Y GGAAUGAAAUGCUUUGAAA NM_004654 3858 USP9Y GGUUAUAUCUAGUGUAUCA NM_004654 3859 USP9Y GAACAGUAUUCUUGCAAUU NM_004654 3860 USP9Y GCAGAGAGCUUGGAGAUAA NM_004654 3861 USP9Y CAGAAGAGGUGGUGGAAUG NM_004654 3862 USP9Y GUAUUUAAGAAGUGGAGAA NM_004654 3863 USP9Y GAGAUGAUGUAUUUGGAUA NM_004654 3864 USP9Y GGCAAAGAAUGAAGCCAAA NM_004654 3865 USP9Y AAUUAGGGCUAUACAGAAA NM_004654 3866 USP9Y UAACAGAGCUAUAGAUCUU NM_004654 3867 USP9Y AAACACAGCUUCUGAAAUU NM_004654 3868 USP9Y CAGCAUUAAUUGUGCAAGA NM_004654 3869 USP9Y GGACAAGAUGAGACUAUAA NM_004654 3870 USP9Y CCAAGUUACUCAUGAUCAA NM_004654 3871 USP9Y AGGCAAAGAAUGAAGCCAA NM_004654 3872 VCIP135 CAGAAGGACUGGAGUGAUA NM_025054 3873 VCIP135 GGGACAGACUUUAGUAAUA NM_025054 3874 VCIP135 GAUCCAAGAGCUAGGGAAA NM_025054 3875 VCIP135 GGAAGAGUGGUCAGAGAAA NM_025054 3876 VCIP135 CAGCAUGGCGACAGAAUUA NM_025054 3877 VCIP135 CGACAGAAUUACAAUAGAA NM_025054 3878 VCIP135 GCGAAAGGUCAGAGGAGAU NM_025054 3879 VCIP135 AGUAAUAGUUCCACCUAAA NM_025054 3880 VCIP135 AAACAGAAGUUGUGAGUUC NM_025054 3881 VCIP135 CAAUGAAACUUGUUACCAA NM_025054 3882 VCIP135 GGAUAAUCGCCUUCACAAA NM_025054 3883 VCIP135 GGUCAGAGAAACAGUAUAU NM_025054 3884 VCIP135 AGAGAAGUGCACUGGGAAA NM_025054 3885 VCIP135 CCUCAUAGAACCAGAGCAU NM_025054 3886 VCIP135 GACAGAAGUUUGCAAGAUA NM_025054 3887 VCIP135 GGUGAAUUUGGGAGUGAAA NM_025054 3888 VCIP135 UGGAGAUGUUCAAGGACAA NM_025054 3889 VCIP135 CAACAUUCCUCCAUAUUUA NM_025054 3890 VCIP135 UGGCAUGCCUUAAGAGAGA NM_025054 3891 VCIP135 GAAAGUAUAGCCAGAGAAU NM_025054 3892 VCIP135 GAGAAGAAGAUCCGAAUCA NM_025054 3893 VCIP135 UGGUUGAGGCCCAGCGAAA NM_025054 3894 VCIP135 CCGACAACUUCUAAGGAGA NM_025054 3895 VCIP135 GGUCAGAGGAGAUGGGUCU NM_025054 3896 VCIP135 CAGACUAUGGAAUGAGUAA NM_025054 3897 VCIP135 UUGAAGAGAUGGAUAGUCA NM_025054 3898 VCIP135 GAGUAGUAACAAUGAGAGA NM_025054 3899 VCIP135 GUGGAAGAGUGGUCAGAGA NM_025054 3900 VCIP135 GGAUGGUGGUUGUGUUAUU NM_025054 3901 VCIP135 AGGAGUUAAACAUGAGUAA NM_025054 3902 VDU1 CCUCAGAACAUUUGGGAUA NM_015017 3903 VDU1 UGAAAGUAGUAGUCAGAAA NM_015017 3904 VDU1 GAGAAGAUGUGCAAUAAGA NM_015017 3905 VDU1 GGAUGAAGAAGAUGAACUU NM_015017 3906 VDU1 GCUAAAGCAAUGUUGUUAA NM_015017 3907 ZA20D1 GAUCAUGAAUGGAGGAAUA NM_020205 3908 ZA20D1 GCAGCAAGCUCAAGAAGAA NM_020205 3909 ZA20D1 UGAAAGUACUUGAGGAUCA NM_020205 3910 ZA20D1 AGAAGGAGGCAGAGAGGAA NM_020205 3911 ZA20D1 AGGAAAUGAUCCAGCGCUA NM_020205 3912 ZA20D1 CGUUUGAACUGGUGGGUGA NM_020205 3913 ZA20D1 CCAGCAGAGUCGAGGGCAA NM_020205 3914 ZA20D1 CCAUGGAGCAGAAGGAGAA NM_020205 3915 ZA20D1 GCUGAAAGUACUUGAGGAU NM_020205 3916 ZA20D1 GGACAAGAAGAGAGCAGAU NM_020205 3917 ZA20D1 CAGCAGACACAGCAGAAUA NM_020205 3918 ZA20D1 ACUUACAGAUUCAGAGUAU NM_020205 3919 ZA20D1 GGGACAGGGUUGGGAGGAA NM_020205 3920 ZA20D1 CCAUAGUCGUCGUGGCAGA NM_020205 3921 ZA20D1 AGGAGAAGUCAAAGCGAGA NM_020205 3922 ZA20D1 GGGACUUGAUGCUGCGGAA NM_020205 3923 ZA20D1 GCAGCUUCAUAGAGAGAGA NM_020205 3924 ZA20D1 GGAGAAUACCAAGGAACAA NM_020205 3925 ZA20D1 AGGAGAAUACCAAGGAACA NM_020205 3926 RANGB1 GAACAAAUCCGGAGAGAGA NM_017580 3927 RANGB1 CCAAAGACCUAGUGGAACA NM_017580 3928 RANGB1 GAGAGGAAGAUGAGGAUGA NM_017580 3929 RANGB1 GCCCAAAGACCUAGUGGAA NM_017580 3930 RANGB1 ACAAAUCCGGAGAGAGAUA NM_017580 3931 RANGB1 GGAAGUUGCAGUAGUGGUA NM_017580 3932 RANGB1 GAGAGAAGAACAAUGGCAA NM_017580 3933 RANGB1 GGGGAGAAACUUUAGGAUA NM_017580 3934 RANGB1 GUAAUGAGGAACAGCAAGA NM_017580 3935 RANGB1 GCAGGAUAUGCUAGCAAUA NM_017580 3936 RANGB1 UGUCCAGACUCUAGUGCAA NM_017580 3937 RANGB1 CCUAAUAACAUUGAAGCAA NM_017580 3938 RANGB1 GGACUCAGUGCUUCGGAAA NM_017580 3939 RANGB1 GGAUGAUGAAGAUGAAUGA NM_017580 3940 RANGB1 CCGAGGUGCUGGUGCUAAU NM_017580

Thus, consistent with Example XVII, the present invention provides an siRNA that targets a nucleotide sequence for a deubiquitination enzymes, wherein the siRNA is selected from the group consisting of SEQ. ID NOs. 438-3940.

In another embodiment, an siRNA is provided, said siRNA comprising a sense region and an antisense region, wherein said sense region and said antisense region are at least 90% complementary, said sense region and said antisense region together form a duplex region comprising 18-30 base pairs, and said sense region comprises a sequence that is at least 90% similar to a sequence selected from the group consisting of: SEQ. ID NOs 438-3940.

In another embodiment, an siRNA is provided wherein the siRNA comprises a sense region and an antisense region, wherein said sense region and said antisense region are at least 90% complementary, said sense region and said antisense region together form a duplex region comprising 18-30 base pairs, and said sense region comprises a sequence that is identical to a contiguous stretch of at least 18 bases of a sequence selected from the group consisting of: SEQ. ID NOs 438-3940.

In another embodiment, an siRNA is provided wherein the siRNA comprises a sense region and an antisense region, wherein said sense region and said antisense region are at least 90% complementary, said sense region and said antisense region together form a duplex region comprising 19-30 base pairs, and said sense region comprises a sequence that is identical to a contiguous stretch of at least 18 bases of a sequence selected from the group consisting of: SEQ. ID NOs 438-3940.

In another embodiment, a pool of at least two siRNAs is provided, wherein said pool comprises a first siRNA and a second siRNA, said first siRNA comprises a duplex region of length 18-30 base pairs that has a first sense region that is at least 90% similar to 18 bases of a first sequence selected from the group consisting of: SEQ. ID NOs 438-3940 and said second siRNA comprises a duplex region of length 18-30 base pairs that has a second sense region that is at least 90% similar to 18 bases of a second sequence selected from the group consisting of: SEQ. ID NOs 438-3940 and wherein said first sense region and said second sense region are not identical.

In another embodiment, a pool of at least two siRNAs is provided, wherein said pool comprises a first siRNA and a second siRNA, said first siRNA comprises a duplex region of length 18-30 base pairs that has a first sense region that is identical to at least 18 bases of a sequence selected from the group consisting of: SEQ. ID NOs 438-3940 and wherein the second siRNA comprises a second sense region that comprises a sequence that is identical to at least 18 bases of a sequence selected from the group consisting of: SEQ. ID NOs 438-3940.

In another embodiment, a pool of at least two siRNAs is provided, wherein said pool comprises a first siRNA and a second siRNA, said first siRNA comprises a duplex region of length 19-30 base pairs and has a first sense region comprising a sequence that is at least 90% similar to a sequence selected from the group consisting of: SEQ. ID NOs 438-3940, and said duplex of said second siRNA is 19-30 base pairs and comprises a second sense region that comprises a sequence that is at least 90% similar to a sequence selected from the group consisting of: SEQ. ID NOs 438-3940.

In another embodiment, a pool of at least two siRNAs is provided, wherein said pool comprises a first siRNA and a second siRNA, said first siRNA comprises a duplex region of length 19-30 base pairs and has a first sense region comprising a sequence that is identical to at least 18 bases of a sequence selected the group consisting of: SEQ. ID NOs 438-3940 and said duplex of said second siRNA is 19-30 base pairs and comprises a second sense region comprising a sequence that is identical to a sequence selected from the group consisting of: SEQ. ID NOs 438-3940.

In each of the aforementioned embodiments, preferably the antisense region is at least 90% complementary to a contiguous stretch of bases of one of the NCBI sequences identified in Example XVII; each of the recited NCBI sequences is incorporated by reference as if set forth fully herein. In some embodiments, the antisense region is 100% complementary to a contiguous stretch of bases of one of the NCBI sequences identified in Example XVII.

Further, in some embodiments that are directed to siRNA duplexes in which the antisense region is 20-30 bases in length, preferably there is a stretch of 19 bases that is at least 90%, more preferably 100% complementary to the recited sequence id number and the entire antisense region is at least 90% and more preferably 100% complementary to a contiguous stretch of bases of one of the NCBI sequences identified in Example XVII.

While the invention has been described in connection with specific embodiments thereof, it will be understood that it is capable of further modifications and this application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the invention and including such departure from the present disclosure as come within known or customary practice within the art to which the invention pertains and as may be applied to the essential features hereinbefore set forth and as follows in the scope of the appended claims. 

1. An siRNA comprising a sense region and an antisense region, wherein said sense region and said antisense region together form a duplex region, said antisense region and said sense region are each 18-30 nucleotides in length and said antisense region comprises a sequence that is at least 90% complementary to a sequence selected from the group consisting of SEQ. ID NOs. 438-3940.
 2. An siRNA comprising a sense region and an antisense region, wherein said sense region and said antisense region together form a duplex region and said sense region and said antisense region are each 18-30 nucleotides in length, and said antisense region comprises a sequence that is 100% complementary to a contiguous stretch of at least 18 bases of a sequence selected from the group consisting of SEQ. ID NOs. 438-3940.
 3. The siRNA of claim 2, wherein each of said antisense region and said sense region are 19-30 nucleotides in length, and said antisense region comprises a sequence that is 100% complementary to said sequence selected from the group consisting of: SEQ. ID NOs. 438-3940.
 4. A pool of at least two siRNAs, wherein said pool comprises a first siRNA and a second siRNA, said first siRNA comprises a first antisense region and a first sense region that together form a first duplex region and each of said first antisense region and said first sense region are 18-30 nucleotides in length and said first antisense region is at least 90% complementary to 18 bases of a first sequence selected from the group consisting of: SEQ. ID NOs. 438-3940 and said second siRNA comprises a second antisense region and a second sense region that together form a second duplex region and each of said second antisense region and said second sense region are 18-30 nucleotides in length and said second antisense region is at least 90% complementary to 18 bases of a second sequence selected from the group consisting of: SEQ. ID NOs. 438-3940, wherein said first antisense region and said second antisense region are not identical.
 5. The pool of claim 4, wherein said first antisense region comprises a sequence that is 100% complementary to at least 18 bases of said first sequence, and said second antisense region comprises a sequence that is 100% complementary to at least 18 bases of said second sequence.
 6. The pool of claim 4, wherein said first siRNA is 19-30 nucleotides in length and said first antisense region comprises a sequence that is at least 90% complementary to said first sequence, and second siRNA is 19-30 nucleotides in length and said second antisense region comprises a sequence that is at least 90% complementary to said second sequence.
 7. The pool of claim 4, wherein said first antisense region is 19-30 nucleotides in length and said first antisense region comprises a sequence that is 100% complementary to at least 18 bases of said first sequence, and said second antisense region is 19-30 nucleotides in length and said second antisense region comprises a sequence that is 100% complementary to said second sequence.
 8. The siRNA of claim 1, wherein said antisense region and said sense region are each 19-25 nucleotides in length.
 9. The siRNA of claim 4, wherein said first antisense region, said first sense region, said second sense region and said second antisense region are each 19-25 nucleotides in length. 